ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 2009, p. 4069–4079 Vol. 53, No.

10
0066-4804/09/$08.00⫹0 doi:10.1128/AAC.00341-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Efficacy and Safety of Vancomycin versus Teicoplanin:

Systematic Review and Meta-Analysis䌤
Shuli Svetitsky,1 Leonard Leibovici,2 and Mical Paul3*
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel1; Department of Medicine E, Rabin Medical Center, Beilinson Hospital,
and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel2; and Unit of Infectious Diseases, Rabin Medical Center,
Beilinson Hospital, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel3
Received 12 March 2009/Returned for modification 6 April 2009/Accepted 6 July 2009

Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by

Downloaded from http://aac.asm.org/ on October 8, 2020 by guest

invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis
of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for
the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or
publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers
independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using
the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was
similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used
adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials
with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to
10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for
mortality, including the assessment of glycopeptides administered empirically or for proven infections, neu-
tropenia, the participant’s age, and drug dosing. There were no significant differences between teicoplanin and
vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24;
95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were
observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive
organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR,
0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin
is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than
vancomycin.

Methicillin (meticillin)-resistant Staphylococcus aureus
(MRSA) infections are a serious and constantly growing public
health concern. The incidence of invasive MRSA infections in
the United States was estimated to be 31.8 per 100,000 popu-
lation in the general population in 2005, with a fatality rate of
6.3/100,000 population (32). The percentage of MRSA isolates
among all S. aureus bloodstream isolates in hospitals was 49%
in United States hospitals (1998 to 2005), with little variability
in that proportion occurring between regions (68). In Europe,
the proportions ranged from less than 1% in northern coun-
tries to ⬎50% in southern countries (1999 to 2007) (17). Com-
munity-acquired MRSA is now of growing concern, reaching
rates of more than 80% of all community-acquired S. aureus
infections in certain locations in the United States (5, 31, 37).
The first-line treatment of choice for invasive MRSA infec-
tions is a glycopeptide antibiotic (43). Vancomycin (a glyco-
peptide) and teicoplanin (a lipoglycopeptide) are naturally oc-
curring substances whose bactericidal activity is mediated
mainly by the inhibition of peptidoglycan synthesis of the bac-
terial cell wall. Their spectrum of coverage is similar except for
VanB vancomycin-resistant enterococci that are susceptible to
* Corresponding author. Mailing address: Unit of Infectious Dis-
eases, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100,
Israel. Phone: 972-3-9377512. Fax: 972-3-9377513. E-mail: paulm
@post.tau.ac.il.
䌤
Published ahead of print on 13 July 2009.
teicoplanin (19, 30, 47). Teicoplanin is not approved for use in
the United States, while in Europe it is as commonly used as
vancomycin (2, 3, 69).
The comparative clinical efficacies and toxicity profiles of
vancomycin and teicoplanin are not established. In a previous
review, vancomycin and teicoplanin were found to be equally
efficacious, with teicoplanin causing fewer adverse effects than
vancomycin (76). Since then, the findings of more trials com-
paring vancomycin and teicoplanin have been published. We
performed a systematic review and meta-analysis of random-
ized controlled trials that compared vancomycin to teicoplanin.
The objectives of our review were to compare the efficacy and
safety of these glycopeptides.
MATERIALS AND METHODS
Inclusion criteria. We included randomized or quasirandomized controlled
trials that compared systemic treatment with vancomycin versus teicoplanin for
suspected or proven infections in adults and children. We included both neutro-
penic and nonneutropenic patients. Additional antibiotic treatment was permit-
ted, provided that the same antibiotic and dose or the same rules regarding
additional antibiotics were applied in both study arms.
Outcomes. The primary outcome assessed was all-cause mortality and was
preferentially extracted at day 30. Secondary outcomes included clinical failure,
defined as a nonresolved infection, treatment modification, or death due to the
infection; microbiological failure, defined as the persistence or the reappearance
of the initiating pathogen during treatment, as defined in the study (after day 3);
relapse, defined as the reisolation of the initiating pathogen after the completion
of treatment; superinfection, defined as the development of a different infection
during treatment or within 1 week of the discontinuation of treatment; resistance

4069
4070 SVETITSKY ET AL.
development, defined as the isolation of glycopeptide-resistant gram-positive
bacteria; and adverse events, including adverse events requiring the discontinu-
ation of treatment, nephrotoxicity (as defined in the study), red man syndrome,
and rash.
Search strategy. We searched the Cochrane Register of Controlled Trials,
PubMed, and LILACS databases. Unpublished trials were sought in the refer-
ences of all selected studies; the conference proceedings of the Interscience
Conference on Antimicrobial Agents and Chemotherapy, the European Con-
gress of Clinical Microbiology of Infectious Diseases, and the Infectious Diseases
Society of America; trial registries; ongoing trial databases; and personal con-
tacts with the investigators of the trials included. No language or date restrictions
were imposed. The last search of all sources was performed in June 2008. The
terms “glycopeptides” and “chemical” and the generic and trade names of van-
comycin and teicoplanin were searched for, in combination with the use of the
Cochrane filter for randomized controlled trials in PubMed (28).
Review methods. Two reviewers (S.S. and M.P.) independently applied the
inclusion criteria and extracted the data. We identified the intention-to-treat
population of each trial (all randomized participants), all patients treated per
protocol, and microbiologically evaluable patients. Outcomes were extracted
preferentially or imputed for the intention-to-treat population. Whenever data
were missing, we contacted the authors and primarily requested data on the trial
methods used and the primary outcome. We assessed the risk of bias in the
studies included using domain-based evaluation. The domains assessed included
sequence generation, allocation concealment, blinding, early stopping, selective
reporting, patient attrition, the number of patients excluded from the analysis,
and unit-of-analysis errors (recruitment of patients more than once or reporting
of more than one outcome per patient without adjustment for multiple testing).
Each domain was scored as adequate, unclear, or inadequate by using the criteria
suggested in the Cochrane handbook (28). We judged that allocation conceal-
ment for all outcomes and double blinding for outcomes other than mortality
carried the highest risk for bias and thus report on sensitivity analyses for these
domains.
Statistical analysis. Risk ratios (RRs) for individual studies were calculated
with 95% confidence intervals (CIs). RRs of ⬎1 favor vancomycin. Heterogene-
ity was assessed by the chi-square test (P ⬍ 0.1) and the I2 measure of incon-
sistency (I2 ⬎ 50%). Meta-analyses were conducted by using the fixed-effect
model, unless significant heterogeneity was present, in which case the random-
effects model was used. The effects of risk of bias assessment are reported as
subgroup differences on the basis of a fixed-effect inverse variance meta-analysis
(15). Small-study effects were assessed through visual inspection of funnel plots.
Analyses were conducted by using the RevMan (version 5) program (Nordic
Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark, 2008).
RESULTS
The trial flow is depicted in Fig. 1. The search yielded 269
publications, 61 of which were potentially eligible; and 24 in-
dividual randomized controlled trials comparing vancomycin
versus teicoplanin fulfilled inclusion criteria (1, 4, 8, 10, 11, 14,
18, 20, 22, 33, 34, 40, 42, 45, 46, 48, 49, 51, 60, 62, 71–72, 77).
The trials were conducted between 1986 and 2007 and in-
cluded a total of 2,332 patients (Table 1). Twelve trials ad-
dressed patients with febrile neutropenia, and the assigned
treatment was mainly empirical (Fig. 1). Twelve studies re-
cruited patients without neutropenia, and treatment was initi-
ated mostly for suspected or documented infections with gram-
positive bacteria. Three trials recruited patients with MRSA
infections only or mostly, one trial recruited patients with me-
thicillin-sensitive S. aureus (MSSA) infections only, and the
median prevalence of MRSA infections in the other studies
reporting on MRSA was 2% (range, 0 to 26%). MRSA isolates
were reported to be susceptible to glycopeptides, but the stud-
ies used various breakpoint definitions, depending on the year
of the study. The median rate of bacteremia in 17 trials report-
ing on the number of patients with bacteremia was 50% (range,
12.5 to 100%). Children alone were assessed in four trials, and
adults and children were assessed in one trial; all other trials
ANTIMICROB. AGENTS CHEMOTHER.
addressed patients ⬎12 years of age. Patients with renal failure
were excluded from 17 trials.
Four trials were performed prior to Eli Lilly’s launch of
purified vancomycin in 1990 (8, 11, 62, 72), and in one study
the purified preparation was introduced during the trial (71).
The standard dosing of teicoplanin for adults was 400 mg/day
for adults and 10 to 12 mg/kg of body weight/day for children,
following a loading dose (Table 1); lower doses (200 mg/day)
were used for adults during the first part of the study in three
trials (45, 62, 71). The intramuscular administration of teico-
planin was permitted in four trials. Monitoring of serum van-
comycin and teicoplanin levels was explicitly stated in 12 and
11 trials, respectively. None of the trials stated the target serum
level. The serum drug levels achieved during the trial were
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
reported in seven trials; median trough values for teicoplanin
and vancomycin were 8.8 ␮g/ml (range, 4.7 to 15.9 ␮g/ml) and
8.2 ␮g/ml (range, 8 to 14.3 ␮g/ml), respectively.
Adequate allocation generation and concealment were de-
scribed in 11 trials. Three additional trials described only ad-
equate allocation generation, and four trials described only
adequate allocation concealment. Two trials were triple
blinded, three were double blinded, and the remaining trials
were open label. In eight trials, unit-of-analysis errors were
detected (Table 1). The full data for one trial were provided by
the authors (1). Additional data on methods or outcomes were
obtained for 11 trials.
All-cause mortality. Eighteen trials reported all-cause mor-
tality at the end of follow-up (14 to 50 days). Mortality was
similar for teicoplanin and vancomycin (RR, 0.95; 95% CI,
0.74 to 1.21) (Fig. 2). No significant heterogeneity was detected
for the overall comparison (P ⫽ 0.57, I2 ⫽ 0%). There were no
statistically significant differences between teicoplanin and
vancomycin among neutropenic and nonneutropenic patients,
by empirical treatment and treatment of suspected or proven
infections caused by gram-positive bacteria, for adults and chil-
dren, for different teicoplanin dosing regimens, for different
types of vancomycin preparations, and with or without drug
level monitoring (Table 2). There was no statistically signifi-
cant difference in mortality in the subgroups of patients with
bacteremia caused by gram-positive bacteria (RR, 1.84; 95%
CI, 0.65 to 5.18; six studies and 158 patients).
When the results were stratified according to the method-
ological quality of the studies, divergent results were observed
(Fig. 2). With adequate methods for concealment of the allo-
cation sequence, the RR for mortality was 0.82 (95% CI, 0.63
to 1.06) in favor of teicoplanin, while unknown methods or
inadequate concealment resulted in an RR of 3.61 (95% CI,
1.27 to 10.30) significantly in favor of vancomycin (P ⫽ 0.01 for
difference between subgroups). However, the studies with a
higher risk of bias included more patients with S. aureus bac-
teremia (median, 100%; range, 62 to 100%) than the low-risk
studies did (median, 45.5%; range, 20 to 100%). In four dou-
ble-blind trials, the RR was 0.48 (95% CI, 0.22 to 1.07), while
in open trials it was 1.04 (95% CI, 0.80 to 1.36). There was no
evidence of the small-study effect overall (Fig. 3).
Secondary outcomes. No significant difference between
teicoplanin and vancomycin with regard to clinical failure was
shown overall (RR, 0.92; 95% CI, 0.81 to 1.05; 21 trials and
1,729 patients). RRs tended to be in favor of teicoplanin for
the nonneutropenic subgroup of patients, when treatment was
VOL. 53, 2009
FIG. 1. Trial flow. RCTs, randomized controlled trials; CR, catheter related; IVDU, intravenous drug abuse. Three publications described two
trials each (22, 55, 66).
initiated for a suspected or a proven infection with gram-
positive bacteria, with higher doses of teicoplanin, and with
adequate allocation concealment and double blinding (Table
2). A modified intention-to-treat analysis, with the assumption
of treatment failure for all dropouts (excluding studies in which
the number randomized was unclear), yielded an RR of 0.94
(95% CI, 0.84 to 1.05; 17 trials and 1,679 patients). Clinical
failure could also be assessed in the subgroups of patients with
documented S. aureus infections (RR, 0.97; 95% CI, 0.63 to
1.51; 13 trials and 289 patients), MRSA infections (RR, 0.67;
VANCOMYCIN VERSUS TEICOPLANIN 4071
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
95% CI, 0.26 to 1.72; 5 trials and 73 patients), and bacteremia
(RR, 0.95; 95% CI, 0.73 to 1.24; 15 trials and718 patients).
The microbiological failure rates were not significantly dif-
ferent for teicoplanin treatment and vancomycin treatment
(RR, 1.24; 95% CI, 0.93 to 1.65; 12 trials and 716 patients). No
significant differences in the rates of relapse (RR, 0.61; 95%
CI, 0.29 to 1.30; 8 trials and 330 patients) and superinfection
(RR, 1.02; 95% CI, 0.77 to 1.37; 10 trials and 1,083 patients)
were found. None of the trials reported quantitatively on the
changes in the glycopeptide MICs for persisting gram-positive
 TABLE 1. Characteristics of included trials
4072

Author(s), yr of Daly dose (no. of participants) Allocation

Main inclusion criteriaa Participant’s ageb % MRSA Blindingd Unit-of-analysis errors
study (reference) Vancomycin Teicoplanin concealmentc

Akan, 2008 (1) 1 g two times for adults, 400 mg two times (three Febrile neutropenia, with solid Adults and children Unknown A Open
10 mg/kg four times doses) and then 400 malignancies; empirical over age 2
for children (97) mg once for adults; 10 first-line treatment
mg/kg two times (three
doses) and then 10 mg/
kg once for children
aged 2–16 yr (93)
Auperin et al., 10 mg/kg four times (34) 10 mg/kg two times (three Febrile neutropenia with solid Children; median age, 8 Unknown A Open
SVETITSKY ET AL.

1997 (4) doses) and then 10 mg/ malignancies; empirical

kg times once (33) first-line treatment
Charbonneau et 12 mg/kg two times or 8 6 mg/kg two times (three Serious GP infection T, mean, 56.8 (range, Unknown B Open
al., 1994 (8) mg/kg three times doses) and then 6 mg/kg 18–87); V, mean,
(32) once (24) 56.4 (range, 20–79)
Contra et al., 1995 10 mg/kg four times (35) 10 mg/kg two times (three Febrile neutropenia; empirical Children Unknown B Open No. of patients randomized
(10) doses) and then 10 mg/ second-line treatment not stated; study
kg once (28) referred to evaluated
patients
Cony-Makhoul et 15 mg/kg two times (35) 6 mg/kg two times (three Febrile neutropenia with T, mean, 51.5 (range, Unknown B Open Patients randomized more
al., 1990 (11) doses) and then 6 mg/kg hematological malignancies; 17–60); V, mean, 45 than once; no. of
once (24) empirical second-line (range, 16–80) patients randomized
treatment reported; clinical failure
reported per episode
only
D’Antonio et al., 15 mg/kg two times (77) 6 mg/kg two times in 48 h Febrile neutropenia with T, mean, 41.5 ⫾ 16.6; Unknown A DB
2004 (14) and then once (77) hematological malignancies V, mean, 37.2
and GP bacteremia ⫾ 15.6
Figuera et al., 1 g two times (85) 400 mg two times (three Febrile neutropenia with T, median, 35 (range, 0 B Open Patients randomized more
1996 (18) doses) and then 400 mg hematological malignancies; 13–68); V, median, than once; no. of
once (68) empirical first-line 39 (range, 13–68) patients randomized not
treatment reported; results
reported per episode
Fortun et al., 2001 500 mg four times (11) 24 mg/kg once (one dose) Intravenous drug abusers T, mean, 31 (range, 21– 0 B Open
(20) and then 12 mg/kg once (most with HIV), with 43); V, mean, 25
(12) right-sided MSSA (range, 18–31)
endocarditis
Gilbert et al., 1991 15 mg/kg two times (27) 6 mg/kg two times (three Trial I, GP bacteremia, except T, mean, 51 ⫾ 17; V, 0 A DB
(two trials) (22) doses) and then 6 mg/kg catheter-associated mean, 61.9 ⫾ 18
once (27) infection; trial 2, catheter-
associated GP bacteremia
Kureishi et al., 15 mg/kg two times (27) 6 mg/kg two times (three Febrile neutropenia with T, median, 40 (range, Unknown A TB
1991 (33) doses) and then 6 mg/kg hematological malignancies; 19–80); V, median,
once (26) empirical first-line 38 (range, 20–76)
treatment
Liu et al., 1996 500 mg four times (20) 400 mg two times (three Documented MRSA T, mean, 71 (range, 36– 100 C Open No. of patients randomized
(34) doses) and then 400 mg bacteremia 88); V, mean, 67 not stated; study
once (20) (range, 24–82) referred to evaluated
patients
Menichetti et al., 15 mg/kg two times 8 mg/kg once (one dose) Febrile neutropenia with T, mean, 44 (range, 14– 2 A/B Open
1994 (40) (303) and then 6 mg/kg once hematological malignancies; 78); V, mean, 42
(332) empirical first-line (range, 14–72)
treatment
Nadal et al., 1999 40 mg/kg three times 10 mg/kg once (25) Children in pediatric/neonatal Children and neonates; Unknown A Open
(42) (22) ICU with suspected or T, mean, 39 wk; V,
proven GP infection mean, 52 wk
ANTIMICROB. AGENTS CHEMOTHER.

Downloaded from http://aac.asm.org/ on October 8, 2020 by guest

Neville et al., 1995 1 g two times; for 400 mg once (5 patients Most patients with malignancy T, median, 38 (range, 3 A Open Patients randomized more
(45) patients weighing less received 400 mg once in with suspected or proven 18–71); V, median, than once; no. of
than 50 kg, 750 mg the first 24 h and then GP infection 32 (range, 18–69) patients randomized in
two times (29) 200 mg once) (28) trial reported; clinical
failure reported per
VOL. 53, 2009

episode only
Nucci et al., 1998 40 mg/kg/day divided 6 mg/kg two times (three Febrile neutropenia, T, median, 31 (range, 1 A Open Patients randomized more
(46) into four doses a day doses) and then 6 mg/kg hematological malignancies; 13–71); V, median, than once; no. of
(53) once (53) empirical first-line 37 (range, 12–72) patients randomized to
treatment each arm reported;
clinical failure and
adverse events reported
per episode
Pham Dang et al., Target drug levels 400 mg two times for 36 h, Postorthopedic surgery bone T, mean, 62 ⫾ 17; V, 70 A Open
2001 (48) between 20 and 30 followed by 400 mg infections caused mainly by mean, 64 ⫾ 23
mg/liter (15) once; target levels, ⱖ10 MRSA
mg/liter (15)
Rolston et al., 15 mg/kg two times 6 mg/kg two times (three Catheter-related or other T, mean, 50 (range, 19– 2 A TB
1999 (51) (122) doses) and then 6 mg/kg vascular access-related GP 80); V, mean, 50
once (118) bacteremia (range, 17–83)
Sidi et al., 2000 40 mg/kg in three 10 mg/kg two times (three Febrile neutropenia with GP Children; T, mean, 8 Unknown C Open Patients randomized more
(60) divided doses a day doses) and then 10 mg/ bacteremia (range, 2–14); V, than once; no. of
(21) kg once (24) mean, 8.5 (range, patients randomized
2.5–15) reported; clinical failure
reported per episode
only
Smith et al., 1989 1 g two times (35) For first 11 episodes, 400 Febrile neutropenic patients T, mean, 40 (range, 17– Unknown A Open Patients randomized more
(62) mg once (one dose) and with hematological 77); V, mean, 45 than once; no. of
then 200 mg once; for malignancy and catheter- (range, 26–78) patients randomized to
subsequent episodes, associated GP infections each arm not reported;
800 mg once (one dose) results reported per
and then 400 mg once episode
(37)
Van der Auwera 1 g two times (37) 400 mg once (three doses) Cancer patients without T, median, 59 (range, 5 A Open
et al., 1991 (71) and then 200 mg once neutropenia with 35–78); V, median,
and 400 mg once (37) documented GP infection 62 (range, 25–75)
Van Laethem et 1 g two times (10) 400 mg once (12) Documented MRSA infections T, mean, 56 (range, 23– 100 B Open Patients randomized more
al., 1988 (72) 85); V, mean, 69 than once; no. of
(range, 44–86) patients randomized and
evaluated for each
outcome reported
Vazquez et al., Variable, according to 400 mg two (three doses) Febrile neutropenic patients T, mean, 51; V, mean, Unknown A/B Open Patients randomized more
1999 (73) nomogram (38) and then 400 mg once with hematological 47 than once; no. of
(38) malignancies; empirical patients randomized to
second-line treatment each arm not reported;
results reported per
episode
Zhao et al., 2003 1 g two times (34) 400 mg two times and then Documented GP infections T, mean, 41.9 ⫾ 16; V, 20 B Open
(77) 400 mg once (36) mean, 40.6 ⫾ 14.2
a
GP, gram-positive organism; HIV, human immunodeficiency virus; ICU, intensive care unit; VAP, ventilator-associated pneumonia. Empirical treatment for febrile neutropenia given as first-line treatment (initial
empirical treatment) or second-line treatment (for persistent fever unresponsive to the first-line regimen).
b
Ages are given in years unless otherwise stated. T, teicoplanin; V, vancomycin.
c
A, adequate allocation concealment methods ensuring that intervention allocations could not have been foreseen in advance of, or during, enrollment; B, unreported or unclear methods; C, inadequate allocation
concealment methods whereby intervention allocations could be foreseen in advance of, or during, enrollment.
d
DB, double blind; TB, triple blind.
VANCOMYCIN VERSUS TEICOPLANIN
4073

Downloaded from http://aac.asm.org/ on October 8, 2020 by guest

4074 SVETITSKY ET AL.
FIG. 2. All-cause mortality for trials. Trials are subgrouped by the methods of allocation concealment used in the trial. M-H, Mantel-Haenszel.
bacteria. Seven trials reported qualitatively that no resistant
isolates were detected, except in 3/68 patients in one trial (18)
who acquired teicoplanin-resistant isolates following treatment
with teicoplanin.
Adverse events. The overall number of adverse events was
reported in all trials except the unpublished trial (1). There
were significantly fewer total adverse events for teicoplanin
than for vancomycin, when they were reported as the number
of adverse event episodes per patient episode (RR, 0.61; 95%
CI, 0.50 to 0.74; 23 trials and 2,046 patient episodes) and when
they were reported as the number of patients experiencing at
least one adverse event per patient (RR, 0.57; 95% CI, 0.45 to
0.72; 19 trials and 1,641 patients). There were significantly
fewer adverse events requiring the discontinuation of treat-
ment with teicoplanin (RR of 0.54 and 95% CI of 0.33 to 0.87
for 13 trials and 904 patient episodes; RR of 0.59 and 95% CI
of 0.36 to 0.97 for 12 trials and 829 patients). There was
significantly less nephrotoxicity reported for teicoplanin (Fig.
4) (RR of 0.44 and 95% CI of 0.32 to 0.61 for 21 trials and
1,992 patient episodes; RR of 0.33 and 95% CI of 0.22 to 0.50
for 17 trials and 1,587 patients). Nephrotoxicity was defined
heterogeneously as creatinine levels above the normal range
(1.1 to 1.5 mg/dl), by an absolute increase of 0.5 mg/dl or as a
50% to 100% increase from the baseline level. Similar RRs
were observed in studies that recruited children, although none
ANTIMICROB. AGENTS CHEMOTHER.
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
of the differences were statistically significant among children
alone (RR for any adverse event, 0.53 [95% CI, 0.24 and 1.18;
four trials and 216 children]; RR for adverse events requiring
discontinuation, 0.66 [95% CI, 0.11 and 3.9; two trials and 147
children]; RR for nephrotoxicity, 0.31 [95% CI, 0.09 to 1.07;
three trials and 197 children]). Severe nephrotoxicity, defined
as the need for hemodialysis, was reported only with vancomy-
cin and among adults (RR, 0.16; 95% CI, 0.03 to 0.86; eight
trials and 341 patients [events were reported in three trials]).
There were no cases of red man syndrome in the teicoplanin
group, whereas there was a 5% incidence of red man syndrome
in the vancomycin group (RR of 0.21 and 95% CI of 0.08 to
0.54 for 10 trials and 756 episodes and RR of 0.24 and 95% CI
of 0.08 to 0.76 for 7 trials and 500 patients); this outcome was
assessed only among adults. The occurrence of other rash was
not significantly different between the groups (RR of 0.74 and
95% CI of 0.49 to 1.12 for 16 trials and 1,707 episodes; RR of
0.65 and 95% CI of 0.41 to 1.03 for 12 trials and 1,398 pa-
tients).
Nephrotoxicity was less frequent with teicoplanin in trials
with both purified and unpurified vancomycin (Fig. 4) and both
in studies that reported routine monitoring of vancomycin lev-
els (RR, 0.31; 95% CI, 0.18 to 0.51; 9 studies and 663 episodes)
and in those that did not (RR, 0.60; 95% CI, 0.38 to 0.95; 12
studies and 1,329 episodes). In a further sensitivity analysis that
VOL. 53, 2009 VANCOMYCIN VERSUS TEICOPLANIN 4075

TABLE 2. Subgroup analyses for vancomycin versus teicoplanin 0.50), which translates into a number needed to harm (NNH)
RR (95% CI), no. of studies
of 14 (95% CI, 11 to 25) patients. This effect was not associated
Characteristic included in analysis with the year of the study or drug level monitoring. The effect
All-cause mortality Clinical failure
was similar when the analysis was limited to trials that used the
currently available purified preparation of vancomycin (RR,
Study population 0.44 [95% CI, 0.30 to 0.65]; NNH, 20 [95% CI, 14 to 33]).
Neutropenic patients 0.95 (0.68, 1.34), 9 0.98 (0.83, 1.16), 9
Comparative assessment for the development of resistance
Nonneutropenic 0.94 (0.66, 1.32), 9 0.84 (0.68, 1.03), 12
patients is of interest in an era of glycopeptide resistance, especially
Treatment when a policy of using one or another glycopeptide is being
administration considered. It is an important untoward effect of antibiotic
Empirical 0.92 (0.65, 1.30), 7 0.97 (0.82, 1.15), 8 therapy with implications for the individual treated and future
Semiempirical/ 0.99 (0.70, 1.39), 11 0.86 (0.71, 1.05), 13
definitive patients. Randomized controlled trials provide a well-con-
Age group trolled framework for its assessment. However, resistance de-
Adults mostly 0.92 (0.71, 1.19), 15 0.92 (0.81, 1.05), 18 velopment was poorly reported in all trials, both old and new.

Downloaded from http://aac.asm.org/ on October 8, 2020 by guest

Children mostly 1.26 (0.48, 3.30), 3 1.27 (0.35, 4.62), 3 None of the trials compared quantitatively the changes in
Teicoplanin dose
MICs of the persisting S. aureus isolates. Qualitatively, several
Standard/high 0.96 (0.70, 1.31), 16 0.91 (0.79, 1.05), 18
Low 0.92 (0.65, 1.31), 2 0.96 (0.63, 1.47), 3 trials comparing teicoplanin to vancomycin reported that re-
Vancomcyin preparation sistance development was null. However, the definitions of
Purified 0.93 (0.68, 1.28), 15 0.90 (0.78, 1.03), 16 “resistance” have changed since the years that those studies
Unpurified 0.98 (0.69, 1.39), 3 1.02 (0.55, 1.91), 5 were conducted, following CLSI breakpoint definitions (70).
Drug level monitoringa
Yes 0.77 (0.55, 1.09), 9 0.86 (0.70, 1.05), 11 While susceptibility to vancomycin is currently defined as an
No 1.10 (0.77, 1.57), 9 0.97 (0.82, 1.15), 10 MIC of ⱕ2 ␮g/ml, the breakpoints used in the older studies
Allocation concealment ranged from 4 to 8 ␮g/ml. Thus, we do not have information on
Adequate 0.82 (0.63, 1.06), 13 0.88 (0.76, 1.03), 12 the emergence of S. aureus strains with MICs of ⬎2 ␮g/ml from
Unclear 3.29 (0.98, 11.05), 3 1.14 (0.88, 1.47), 6
randomized trials comparing vancomycin to teicoplanin. Re-
Inadequate 4.66 (0.57, 37.70), 2 0.73 (0.34, 1.56), 3
Blinding sistance to teicoplanin emerges sooner than resistance to van-
Double/triple blind 0.48 (0.22, 1.07), 5 0.86 (0.67, 1.10), 4 comycin in S. aureus strains in observational studies and case
Other 1.04 (0.80, 1.36), 13 0.95 (0.81, 1.10), 17 reports (38, 39, 50); however, the culprit antibiotic inducing
a
Monitoring of drug levels for both vancomycin and teicoplanin. glycopeptide resistance in clinical isolates was usually vanco-
mycin (61).
The main limitation of the available evidence is the paucity
excluded all trials published prior to 1994, the results were of patients with MRSA infections in existing trials. This limited
similar (RR for nephrotoxicity, 0.48; 95% CI, 0.32 to 0.72; 15 the ability of the primary studies and our analysis to assess
trials and 1,662 episodes), and there was no significant associ- clinical and microbiological efficacy for the treatment of
ation by meta-regression analysis between the year of the trial’s MRSA infections (the rate of mortality for patients infected
start and the total number of adverse events or nephrotoxicity with MRSA was reported in a single trial [72]), to stratify the
(P ⫽ 0.28 and P ⫽ 0.73, respectively). Similarly, there was no analyses by the baseline isolates’ susceptibility, and to ade-
association between trial size and effects (Fig. 3). quately assess the development of resistance. However, the
trials recruited mostly septic patients, who are commonly given
glycopeptides (at least empirically) in clinical practice. Data on
DISCUSSION
mortality were incomplete and were available for only 17/24
We compared the efficacy and safety of the glycopeptides trials; the authors could not supply further data since the trials
currently in use, teicoplanin and vancomycin. All-cause mor- were old. We noted a divergence in the results by randomiza-
tality was the primary outcome, since this outcome is the most tion method that can be explained by a true effect (the better
objective and its prevention is the primary motivation for the efficacy of teicoplanin) or by the association between studies
treatment of severe infections. with a higher risk for bias and sicker patients, as reflected by
There was no significant difference in all-cause mortality the higher percentage of patients with bacteremia in higher-
between teicoplanin and vancomycin overall. In studies report- risk studies (in this case, indicating the better efficacy of van-
ing adequate allocation concealment (thus ensuring appropri- comycin). Unbalanced randomization (allocating less seriously
ate randomization), there was a trend in favor of teicoplanin, ill patients to teicoplanin with inadequate methods for con-
while studies with unclear or inadequate allocation conceal- cealment) is another possibility, although we did not find a
ment showed a significant advantage for vancomycin. The lat- difference in baseline patient characteristics (data not shown).
ter studies recruited more patients with bacteremia. There Increasing MICs for vancomycin have been observed in S.
were no significant differences between teicoplanin and vanco- aureus isolates over the last decade and is termed “MIC creep”
mycin with regard to clinical failure, microbiological failure, (64). Increasing MICs, in turn, have been associated with van-
and other secondary efficacy outcomes. There were signifi- comycin treatment failures, even within the currently defined
cantly fewer adverse events with teicoplanin than with vanco- susceptible range (MIC ⱕ 2 ␮g/ml). MICs of 2 ␮g/ml and even
mycin, including events requiring the discontinuation of treat- between 1 and 2 ␮g/ml were significant and independent pre-
ment, nephrotoxicity, and red man syndrome. The effect dictors of treatment failure in observational studies (27, 35, 41,
estimate for nephrotoxicity was an RR of 0.33 (95% CI, 0.22 to 58, 63). This has led to recommendations regarding vancomy-
4076 SVETITSKY ET AL.
FIG. 3. Funnel plots. (A) All-cause mortality; (B) nephrotoxicity. RRs are plotted against standard errors, as a measure of the study’s precision.
cin level monitoring and dosing. For complicated infections
(bacteremia, endocarditis, osteomyelitis, meningitis, and hos-
pital-acquired pneumonia) and for infections caused by strains
with MICs of ⬎1 ␮g/ml, trough levels of 15 to 20 ␮g/ml are
recommended (56). The usual dosing strategies are insufficient
to achieve these concentrations in patients with normal renal
function, and doses of vancomycin up to 4 g/day are necessary.
ANTIMICROB. AGENTS CHEMOTHER.
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
As these doses are associated with increased nephrotoxicity
(36), monitoring of trough serum levels is recommended (56).
Similar data for teicoplanin are largely lacking. A mean daily
dose of 4 mg/kg was associated with treatment failure when
compared to a mean daily dose of 6 mg/kg, but even the higher
dose resulted in low mean trough levels of 7.8 ⫾ 4.8 ␮g/ml (24).
Doses of 6 mg/kg twice daily achieved serum concentrations of
VOL. 53, 2009
FIG. 4. Nephrotoxicity. Trials are subgrouped by the type of vancomycin preparation used in the trial: trials that used purified vancomycin and
those reporting on the use of unpurified vancomycin for part or all of the trial. Similar results were obtained when the results for one trial published
in 1991 were removed from the unpurified subgroup. M-H, Mantel-Haenszel.
⬎10 ␮g/ml by the second day of treatment. Thus, the admin-
istration of teicoplanin loading doses of 6 mg/kg twice daily for
48 h has been recommended for all infections, and for com-
plicated infections, continuation of the high-dose regimen is
recommended (6). Notably, in our review demonstrating the
similar efficacies of teicoplanin and vancomycin, once-daily
dosing of teicoplanin was used in all studies.
To resolve the remaining questions on the efficacy and safety
of vancomycin versus those of teicoplanin, a contemporary trial
that uses adequate randomization methods and that recruits
patients with bacteremia (preferably MRSA bacteremia) is
needed. Such a trial is important, given the common use of
these agents and the implication of a policy to use one or
another drug. New lipoglycopeptides targeting improved phar-
macokinetics, antibacterial activity, and spectrum of coverage
against vancomycin-resistant enterococci and staphylococci
have been developed. Telvancin, dalbavancin, and oritavancin
are currently undergoing clinical testing (Fig. 1). Trials assess-
ing both old and new glycopeptides should target patients who
will be given glycopeptides in clinical practice. Skin and soft
tissue infections, which are frequently targeted for the assess-
ment of new antibiotics, constitute a poor choice for the as-
sessment of antibiotic efficacy, since the outcomes do not nec-
essarily depend on the antibiotic treatment. Studies should
address resistance development using sensitive methods for the
detection of glycopeptide resistance (39, 44, 50, 74).
VANCOMYCIN VERSUS TEICOPLANIN 4077
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
Given the similar efficacies teicoplanin and vancomycin and
the lower rate of adverse events with teicoplanin, including
serious adverse events, the use of teicoplanin for the treatment
of infections caused by MRSA and other resistant gram-posi-
tive organisms should be considered. Uncomplicated infections
permit once-daily dosing of teicoplanin and the possibility of
intramuscular injection. Complicated infections probably man-
date higher dosing strategies for both vancomycin and teico-
planin that should be accompanied by monitoring for renal
toxicity, especially with vancomycin.
ACKNOWLEDGMENTS
We thank the authors who responded to our mail and provided
additional data.
We have no conflicts of interest to declare.
This work was performed in partial fulfillment of the M.D. thesis
requirements of the Sackler Faculty of Medicine, Tel Aviv University
(S.S.).
REFERENCES
1. Akan, H. 2008. Comparison of teicoplanin and vancomycin in initial empir-
ical antibiotic regimen for febrile neutropenic patients. Trial NCT00454272.
National Institutes of Health, Bethesda, MD. http://clinicaltrials.gov/.
2. Alfandari, S., C. Bonenfant, L. Depretere, and G. Beaucaire. 2007. Use of 27
parenteral antimicrobial agents in north of France hospitals. Med. Mal.
Infect. 37:103–107.
3. Ansari, F., K. Gray, D. Nathwani, G. Phillips, S. Ogston, C. Ramsay, and P.
Davey. 2003. Outcomes of an intervention to improve hospital antibiotic
prescribing: interrupted time series with segmented regression analysis. J.
Antimicrob. Chemother. 52:842–848.
4078 SVETITSKY ET AL.
4. Auperin, A., C. Cappelli, E. Benhamou, A. Pinna, E. Peeters, C. Atlani, and
O. Hartmann. 1997. Teicoplanin or vancomycin in febrile neutropenic chil-
dren with cancer: a randomized study on cost effectiveness. Med. Mal. Infect.
27:984–988. (In French.)
5. Boucher, H. W., and G. R. Corey. 2008. Epidemiology of methicillin-resistant
Staphylococcus aureus. Clin. Infect. Dis. 46(Suppl. 5):S344–S349.
6. Brink, A. J., G. A. Richards, R. R. Cummins, and J. Lambson. 2008. Rec-
ommendations to achieve rapid therapeutic teicoplanin plasma concentra-
tions in adult hospitalised patients treated for sepsis. Int. J. Antimicrob.
Agents 32:455–458.
7. Bucaneve, G., F. Menichetti, and A. Del Favero. 1999. Cost analysis of 2
empiric antibacterial regimens containing glycopeptides for the treatment of
febrile neutropenia in patients with acute leukaemia. Pharmacoeconomics
15:85–95.
8. Charbonneau, P., I. Harding, J. J. Garaud, J. Aubertin, F. Brunet, and Y.
Domart. 1994. Teicoplanin: a well-tolerated and easily administered alter-
native to vancomycin for gram-positive infections in intensive care patients.
Intensive Care Med. 20(Suppl. 4):S35–S42.
9. Chow, A. W., P. J. Jewesson, A. Kureishi, and G. L. Phillips. 1993. Teico-
planin versus vancomycin in the empirical treatment of febrile neutropenic
patients. Eur. J. Haematol Suppl. 54:18–24.
10. Contra, T., M. Nestora, C. Scaglione, L. Madero, and M. A. Diaz. 1995. A
study of teicoplanin and vancomycin in combination therapy for febrile
episodes in neutropenic paediatric patient. Can. J. Infect. Dis. 6(Suppl.
C):309.
11. Cony-Makhoul, P., G. Brossard, G. Marit, J. L. Pellegrin, J. Texier-
Maugein, and J. Reiffers. 1990. A prospective study comparing vancomycin
and teicoplanin as second-line empiric therapy for infection in neutropenic
patients. Br. J. Haematol. 76(Suppl. 2):35–40.
12. Corey, G. R. 2008. A phase 2, randomized, double-blind, parallel-group,
multinational trial of intravenous ARBELIC (TD 6424) for treatment of
uncomplicated Staphylococcus Aureus bacteremia. Trial NCT00062647. Na-
tional Institutes of Health, Bethesda, MD. http://clinicaltrials.gov/.
13. Corey, G. R., E. Rubinstein, T. Lalani, M. H. Kollef, A. F. Shorr, F. Genter,
B. S. L., and H. D. Friedland on behalf of the Attain Study Group. 2008.
Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Chemother. (ICAAC)-
Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet., abstr. K-528. American
Society for Microbiology and Infectious Diseases Society of America, Wash-
ington, DC.
14. D’Antonio, D., T. Staniscia, R. Piccolomini, G. Fioritoni, S. Rotolo, G.
Parruti, G. Di Bonaventura, A. Manna, V. Savini, M. P. Fiorilli, P. Di
Giovanni, A. Francione, F. Schioppa, and F. Romano. 2004. Addition of
teicoplanin or vancomycin for the treatment of documented bacteremia due
to gram-positive cocci in neutropenic patients with hematological malignan-
cies: microbiological, clinical and economic evaluation. Chemotherapy 50:
81–87.
15. Deeks, J. J., D. G. Altman, and M. J. Bradburn. 2001. Statistical methods for
examining heterogeneity and combining results from several studies in meta-
analysis, p. 285–312. In M. Egger, G. Davey Smith, and D. G. Altman (ed.),
Systematic reviews in health care: meta-analysis in context, 2nd ed. BMJ
Publication Group, London, United Kingdom.
16. Del Favero, A. 1992. The use of glycopeptides as empiric antiobiotic therapy
in febrile neutropenic patients. A comparison between teicoplanin (TEI) and
vancomycin (VAN). The GIMEMA-Infection Program. Leuk-Lymphoma
7(Suppl. 2):110–111.
17. European Antimicrobial Resistance Surveillance System. 2007, posting
date. EARSS annual report 2007. European Antimicrobial Resistance
Surveillance System. http://www.rivm.nl/earss/result/Monitoring_reports
/Annual_reports.jsp.
18. Figuera, A., J. F. Tomas, L. Hernandez, M. L. Jimenez, M. J. Penarrubia,
M. C. del Rey, R. Arranz, R. Camara, J. L. Lopez-Lorenzo, and J. M.
Fernandez-Ranada. 1996. Imipenem combined with teicoplanin or vanco-
mycin in the initial empirical treatment of febrile neutropenia. Analysis of
the primary response and of a global sequential strategy in 126 episodes.
Rev. Clin. Esp. 196:515–522. (In Spanish.)
19. Finch, R. G., and G. M. Eliopoulos. 2005. Safety and efficacy of glycopeptide
antibiotics. J. Antimicrob. Chemother. 55(Suppl. 2):ii5–ii13.
20. Fortun, J., E. Navas, J. Martinez-Beltran, J. Perez-Molina, P. Martin-
Davila, A. Guerrero, and S. Moreno. 2001. Short-course therapy for right-
side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin
versus glycopeptides in combination with gentamicin. Clin. Infect. Dis. 33:
120–125.
21. Giamarellou, H., W. O’Riordan, H. W. Harris, S. Owen, S. Porter, and J.
Loutit. 2003. Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother.,
abstr. L-739a.
22. Gilbert, D. N., C. A. Wood, R. C. Kimbrough, and the Infectious Diseases
Consortium of Oregon. 1991. Failure of treatment with teicoplanin at 6
milligrams/kilogram/day in patients with Staphylococcus aureus intravascular
infection. Antimicrob. Agents Chemother. 35:79–87.
23. Goldstein, B. P., E. Seltzer, R. Flamm, and D. Sahm. 2005. Abstr. 45th
Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-1577.
24. Harding, I., A. P. MacGowan, L. O. White, E. S. Darley, and V. Reed. 2000.
ANTIMICROB. AGENTS CHEMOTHER.
Teicoplanin therapy for Staphylococcus aureus septicaemia: relationship be-
tween pre-dose serum concentrations and outcome. J. Antimicrob. Che-
mother. 45:835–841.
25. Hartman, C. S., M. M. Wasilewski, and B. M. Bates. 2008. Abstr. 48th Annu.
Intersci. Conf. Antimicrob. Agents Chemother. (ICAAC)-Infect. Dis. Soc.
Am. (IDSA) 46th Annu. Meet., abstr. L-1514. American Society for Micro-
biology and Infectious Diseases Society of America, Washington, DC.
26. Hernandez, L., and A. Figuera. 1995. Empiric antibiotic regimen for febrile
neutropenia (FN). Imipenem plus vancomycin vs imipenem plus teicoplanin
as initial therapy. Bone Marrow Transplant. 15:162. (Abstract.)
27. Hidayat, L. K., D. I. Hsu, R. Quist, K. A. Shriner, and A. Wong-Beringer.
2006. High-dose vancomycin therapy for methicillin-resistant Staphylococcus
aureus infections: efficacy and toxicity. Arch. Intern. Med. 166:2138–2144.
28. Higgins, J. P. T., and S. Green. 2008. Cochrane handbook for systematic
reviews of interventions, version 5.0.0, updated February 2008. The Co-
chrane Collaboration, Washington, DC. www.cochrane-handbook.org.
29. Jauregui, L. E., S. Babazadeh, E. Seltzer, L. Goldberg, D. Krievins, M.
Frederick, D. Krause, I. Satilovs, Z. Endzinas, J. Breaux, and W. O’Riordan.
2005. Randomized, double-blind comparison of once-weekly dalbavancin
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
versus twice-daily linezolid therapy for the treatment of complicated skin and
skin structure infections. Clin. Infect. Dis. 41:1407–1415.
30. Kahne, D., C. Leimkuhler, W. Lu, and C. Walsh. 2005. Glycopeptide and
lipoglycopeptide antibiotics. Chem. Rev. 105:425–448.
31. Kallen, A. J., J. Brunkard, Z. Moore, P. Budge, K. E. Arnold, G. Fosheim, L.
Finelli, S. E. Beekmann, P. M. Polgreen, R. Gorwitz, and J. Hageman. 2009.
Staphylococcus aureus community-acquired pneumonia during the 2006 to
2007 influenza season. Ann. Emerg. Med. 53:358–365.
32. Klevens, R. M., M. A. Morrison, J. Nadle, S. Petit, K. Gershman, S. Ray,
L. H. Harrison, R. Lynfield, G. Dumyati, J. M. Townes, A. S. Craig, E. R.
Zell, G. E. Fosheim, L. K. McDougal, R. B. Carey, and S. K. Fridkin. 2007.
Invasive methicillin-resistant Staphylococcus aureus infections in the United
States. JAMA 298:1763–1771.
33. Kureishi, A., P. J. Jewesson, M. Rubinger, C. D. Cole, D. E. Reece, G. L.
Phillips, J. A. Smith, and A. W. Chow. 1991. Double-blind comparison of
teicoplanin versus vancomycin in febrile neutropenic patients receiving con-
comitant tobramycin and piperacillin: effect on cyclosporin A-associated
nephrotoxicity. Antimicrob. Agents Chemother. 35:2246–2252.
34. Liu, C. Y., W. S. Lee, C. P. Fung, N. C. Cheng, C. L. Liu, S. P. Yang, and S. L.
Chen. 1996. Comparative study of teicoplanin vs vancomycin for the treat-
ment of methicillin-resistant Staphylococcus aureus bacteraemia. Clin. Drug
Investig. 12:80–87.
35. Lodise, T. P., J. Graves, A. Evans, E. Graffunder, M. Helmecke, B. M.
Lomaestro, and K. Stellrecht. 2008. Relationship between vancomycin MIC
and failure among patients with methicillin-resistant Staphylococcus aureus
bacteremia treated with vancomycin. Antimicrob. Agents Chemother. 52:
3315–3320.
36. Lodise, T. P., B. Lomaestro, J. Graves, and G. L. Drusano. 2008. Larger
vancomycin doses (at least four grams per day) are associated with an
increased incidence of nephrotoxicity. Antimicrob. Agents Chemother. 52:
1330–1336.
37. Magilner, D., M. M. Byerly, and D. M. Cline. 2008. The prevalence of
community-acquired methicillin-resistant Staphylococcus aureus (CA-
MRSA) in skin abscesses presenting to the pediatric emergency department.
N. C. Med. J. 69:351–354.
38. Mainardi, J. L., D. M. Shlaes, R. V. Goering, J. H. Shlaes, J. F. Acar, and
F. W. Goldstein. 1995. Decreased teicoplanin susceptibility of methicillin-
resistant strains of Staphylococcus aureus. J. Infect. Dis. 171:1646–1650.
39. Maor, Y., G. Rahav, N. Belausov, D. Ben-David, G. Smollan, and N. Keller.
2007. Prevalence and characteristics of heteroresistant vancomycin-interme-
diate Staphylococcus aureus bacteremia in a tertiary care center. J. Clin.
Microbiol. 45:1511–1514.
40. Menichetti, F., P. Martino, G. Bucaneve, G. Gentile, D. D’Antonio, V. Liso,
P. Ricci, A. M. Nosari, M. Buelli, M. Carotenuto, and the Gimema Infection
Program. 1994. Effects of teicoplanin and those of vancomycin in initial
empirical antibiotic regimen for febrile, neutropenic patients with hemato-
logic malignancies.. Antimicrob. Agents Chemother. 38:2041–2046.
41. Moise, P. A., G. Sakoulas, A. Forrest, and J. J. Schentag. 2007. Vancomycin
in vitro bactericidal activity and its relationship to efficacy in clearance of
methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob. Agents
Chemother. 51:2582–2586.
42. Nadal, D., D. Ghelfi, K. Waldvogel, E. Stierli, E. Heitaer, and S. Fanconi.
1999. Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr.
1100, p. 725.
43. Nathwani, D., M. Morgan, R. G. Masterton, M. Dryden, B. D. Cookson, G.
French, and D. Lewis. 2008. Guidelines for UK practice for the diagnosis and
management of methicillin-resistant Staphylococcus aureus (MRSA) infec-
tions presenting in the community. J. Antimicrob. Chemother. 61:976–994.
44. National Committee for Clinical Laboratory Standards. 2007. Performance
standards for antimicrobial susceptibility testing; 17th informational supple-
ment. M100-S17. National Committee for Clinical Laboratory Standards,
Wayne, PA.
45. Neville, L. O., W. Brumfitt, J. M. Hamilton-Miller, and I. Harding. 1995.
VOL. 53, 2009
Teicoplanin vs. vancomycin for the treatment of serious infections: a ran-
domised trial. Int. J. Antimicrob. Agents 5:187–193.
46. Nucci, M., I. Biasoli, S. Braggio, R. Portugal, R. Schaffel, A. Maiolino, M. M.
Loureiro, N. Spector, and W. Pulcheri. 1998. Ceftazidime plus amikacin plus
teicoplanin or vancomycin in the empirical antibiotic therapy in febrile neu-
tropenic cancer patients. Oncol. Rep. 5:1205–1209.
47. Pace, J. L., and G. Yang. 2006. Glycopeptides: update on an old successful
antibiotic class. Biochem. Pharmacol. 71:968–980.
48. Pham Dang, C., F. Gouin, S. Touchais, C. Richard, and G. Potel. 2001. The
comparative costs of vancomycin treatment versus teicoplanin in osteoar-
ticular infection caused by methicillin-resistant staphylococci. Pathol. Biol.
(Paris) 49:587–596. (In French.)
49. Raad, I., R. Darouiche, J. Vazquez, A. Lentnek, R. Hachem, H. Hanna, B.
Goldstein, T. Henkel, and E. Seltzer. 2005. Efficacy and safety of weekly
dalbavancin therapy for catheter-related bloodstream infection caused by
gram-positive pathogens. Clin. Infect. Dis. 40:374–380.
50. Robert, J., R. Bismuth, and V. Jarlier. 2006. Decreased susceptibility to
glycopeptides in methicillin-resistant Staphylococcus aureus: a 20 year study
in a large French teaching hospital, 1983–2002. J. Antimicrob. Chemother.
57:506–510.
51. Rolston, K. V., G. P. Bodey, and A. W. Chow. 1999. Prospective, double-
blind, randomized trial of teicoplanin versus vancomycin for the therapy of
vascular access-associated bacteremia caused by gram-positive pathogens.
J. Infect. Chemother. 5:208–212.
52. Rolston, K. V., H. Nguyen, G. Amos, L. Elting, V. Fainstein, and G. P. Bodey.
1994. A randomized double-blind trial of vancomycin versus teicoplanin for
the treatment of gram-positive bacteremia in patients with cancer. J. Infect.
Dis. 169:350–355.
53. Rubinstein, E., G. R. Corey, H. W. Boucher, M. S. Niederman, A. F.
Shorr, A. Torres, B. S. L., H. D. Friedland, and O. B. O. T. A. S. Group.
2008. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Chemother.
(ICAAC)-Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet., abstr. K-529.
American Society for Microbiology and Infectious Diseases Society of
America, Washington, DC.
54. Rubinstein, E., G. R. Corey, M. E. Stryjewski, H. W. Boucher, R. N. Daly,
F. C. Genter, B. S. L., M. M. Kitt, and H. D. Friedland. 2008. Abstr. 18th
Eur. Congr. Clin. Microbiol. Infect. Dis., abstr. 075.
55. Rubinstein, E., G. R. Corey, M. E. Stryjewski, J. L. Vincent, J. Y. Fagon,
M. H. Kollef, M. M. Kitt, and H. D. Friedland on behalf of the Attain Study
Group. 2008. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Che-
mother. (ICAAC)-Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet., abstr.
K-530. American Society for Microbiology and Infectious Diseases Society of
America, Washington, DC.
56. Rybak, M., B. Lomaestro, J. C. Rotschafer, R. Moellering, Jr., W. Craig, M.
Billeter, J. R. Dalovisio, and D. P. Levine. 2009. Therapeutic monitoring of
vancomycin in adult patients: a consensus review of the American Society of
Health-System Pharmacists, the Infectious Diseases Society of America, and
the Society of Infectious Diseases Pharmacists. Am. J. Health Syst. Pharm.
66:82–98.
57. Rybak, M. J., E. M. Bailey, and L. H. Warbasse. 1992. Absence of “red man
syndrome” in patients being treated with vancomycin or high-dose teicopla-
nin. Antimicrob. Agents Chemother. 36:1204–1207.
58. Sakoulas, G., P. A. Moise-Broder, J. Schentag, A. Forrest, R. C. Moellering,
Jr., and G. M. Eliopoulos. 2004. Relationship of MIC and bactericidal
activity to efficacy of vancomycin for treatment of methicillin-resistant Staph-
ylococcus aureus bacteremia. J. Clin. Microbiol. 42:2398–2402.
59. Seltzer, E., M. B. Dorr, B. P. Goldstein, M. Perry, J. A. Dowell, and T.
Henkel. 2003. Once-weekly dalbavancin versus standard-of-care antimicro-
bial regimens for treatment of skin and soft-tissue infections. Clin. Infect.
Dis. 37:1298–1303.
60. Sidi, V., E. Roilides, E. Bibashi, N. Gompakis, A. Tsakiri, and D. Koliouskas.
2000. Comparison of efficacy and safety of teicoplanin and vancomycin in
children with antineoplastic therapy-associated febrile neutropenia and
gram-positive bacteremia. J. Chemother. 12:326–331.
61. Sievert, D. M., J. T. Rudrik, J. B. Patel, L. C. McDonald, M. J. Wilkins, and
J. C. Hageman. 2008. Vancomycin-resistant Staphylococcus aureus in the
United States, 2002–2006. Clin. Infect. Dis. 46:668–674.
VANCOMYCIN VERSUS TEICOPLANIN 4079
62. Smith, S. R., J. Cheesbrough, R. Spearing, and J. M. Davies. 1989. Ran-
domized prospective study comparing vancomycin with teicoplanin in the
treatment of infections associated with Hickman catheters. Antimicrob.
Agents Chemother. 33:1193–1197.
63. Soriano, A., F. Marco, J. A. Martinez, E. Pisos, M. Almela, V. P. Dimova, D.
Alamo, M. Ortega, J. Lopez, and J. Mensa. 2008. Influence of vancomycin
minimum inhibitory concentration on the treatment of methicillin-resistant
Staphylococcus aureus bacteremia. Clin. Infect. Dis. 46:193–200.
64. Steinkraus, G., R. White, and L. Friedrich. 2007. Vancomycin MIC creep in
non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-
susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates
from 2001–05. J. Antimicrob. Chemother. 60:788–794.
65. Stryjewski, M. E., V. H. Chu, W. D. O’Riordan, B. L. Warren, L. M. Dunbar,
D. M. Young, M. Vallee, V. G. Fowler, Jr., J. Morganroth, S. L. Barriere,
M. M. Kitt, and G. R. Corey. 2006. Telavancin versus standard therapy for
treatment of complicated skin and skin structure infections caused by gram-
positive bacteria: FAST 2 study. Antimicrob. Agents Chemother. 50:862–
867.
Downloaded from http://aac.asm.org/ on October 8, 2020 by guest
66. Stryjewski, M. E., D. R. Graham, S. E. Wilson, W. O’Riordan, D. Young, A.
Lentnek, D. P. Ross, V. G. Fowler, A. Hopkins, H. D. Friedland, S. L.
Barriere, M. M. Kitt, and G. R. Corey. 2008. Telavancin versus vancomycin
for the treatment of complicated skin and skin-structure infections caused by
gram-positive organisms. Clin. Infect. Dis. 46:1683–1693.
67. Stryjewski, M. E., W. D. O’Riordan, W. K. Lau, F. D. Pien, L. M. Dunbar, M.
Vallee, V. G. Fowler, Jr., V. H. Chu, E. Spencer, S. L. Barriere, M. M. Kitt,
C. H. Cabell, and G. R. Corey. 2005. Telavancin versus standard therapy for
treatment of complicated skin and soft-tissue infections due to gram-positive
bacteria. Clin. Infect. Dis. 40:1601–1607.
68. Styers, D., D. J. Sheehan, P. Hogan, and D. F. Sahm. 2006. Laboratory-based
surveillance of current antimicrobial resistance patterns and trends among
Staphylococcus aureus: 2005 status in the United States. Ann. Clin. Micro-
biol. Antimicrob. 5:2.
69. Tacconelli, E., M. Tumbarello, K. G. Donati, M. Bettio, T. Spanu, F. Leone,
L. A. Sechi, S. Zanetti, G. Fadda, and R. Cauda. 2001. Glycopeptide resis-
tance among coagulase-negative staphylococci that cause bacteremia: epide-
miological and clinical findings from a case-control study. Clin. Infect. Dis.
33:1628–1635.
70. Tenover, F. C., and R. C. Moellering, Jr. 2007. The rationale for revising the
Clinical and Laboratory Standards Institute vancomycin minimal inhibitory
concentration interpretive criteria for Staphylococcus aureus. Clin. Infect.
Dis. 44:1208–1215.
71. Van der Auwera, P., M. Aoun, and F. Meunier. 1991. Randomized study of
vancomycin versus teicoplanin for the treatment of gram-positive bacterial
infections in immunocompromised hosts. Antimicrob. Agents Chemother.
35:451–457.
72. Van Laethem, Y., P. Hermans, S. De Wit, H. Goosens, and N. Clumeck. 1988.
Teicoplanin compared with vancomycin in methicillin-resistant Staphylococ-
cus aureus infections: preliminary results. J. Antimicrob. Chemother.
21(Suppl. A):81–87.
73. Vazquez, L., M. P. Encinas, L. S. Morin, P. Vilches, N. Gutierrez, R. Garcia-
Sanz, D. Caballero, and A. D. Hurle. 1999. Randomized prospective study
comparing cost-effectiveness of teicoplanin and vancomycin as second-line
empiric therapy for infection in neutropenic patients. Haematologica 84:
231–236.
74. Walsh, T. R., A. Bolmstrom, A. Qwarnstrom, P. Ho, M. Wootton, R. A. Howe,
A. P. MacGowan, and D. Diekema. 2001. Evaluation of current methods for
detection of staphylococci with reduced susceptibility to glycopeptides.
J. Clin. Microbiol. 39:2439–2444.
75. Wasilewski, M. M., D. P. Disch, J. M. McGill, H. W. Harris, W. O’Riordan,
and M. L. Zeckel. 2001. Abstr. 41st Intersci. Conf. Antimicrob. Agents
Chemother., abstr. UL-18.
76. Wood, M. J. 1996. The comparative efficacy and safety of teicoplanin and
vancomycin. J. Antimicrob. Chemother. 37:209–222.
77. Zhao, W. F., C. H. Ling, and X. F. Zhang. 2003. A randomized controlled
clinical trial of teicoplanin versus vancomycin in the treatment of severe
gram-positive bacterial infections. Jiangsu Med. J. 29:913–915.