Antimicrobial Chemotherapy

Treatment of community-acquired pneumonia

with moxifloxacin: a meta-analysis of
randomized controlled trials
Xin Yuan*1,2, Bei-Bei Liang*3, Rui Wang3, You-Ning Liu1, Chun-Guang Sun3,
Yun Cai4, Xu-Hong Yu3, Nan Bai3, Tie-Mei Zhao1, Jun-Chang Cui1, Liang-An Chen1
1
Department of Respiratory Diseases, General Hospital of Chinese People’s Liberation Army, Beijing, China,
2
Department of Respiration, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China, 3Center
of Medicine Clinical Research, General Hospital of Chinese People’s Liberation Army, Beijing, China,
4
Department of Clinical Pharmacology, General Hospital of Chinese People’s Liberation Army, Beijing, China

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality throughout the world.
To investigate whether moxifloxacin monotherapy is associated with better clinical outcomes than other
antibiotics recommended for CAP among adults with mild-to-moderate or severe CAP, we performed a
meta-analysis. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched for
randomized control trials (RCTs). The efficacy and safety of moxifloxacin were compared with other
antimicrobial agents used to treat CAP. Fourteen RCTs, consisting of 6923 total patients, were included in
the meta-analysis. No difference was found regarding the incidence of adverse events and mortality
between moxifloxacin and the compared regimens. We found that moxifloxacin is as effective and well-
tolerated as other recommended antibiotics for the treatment of CAP and possesses a better pathogen
eradication rate than beta-lactam-based therapy.
Keywords: Community-acquired pneumonia, Meta-analysis, Moxifloxacin

Introduction as the standard therapy of a combination of beta-

Community-acquired pneumonia (CAP) is a common
cause of morbidity and is a potentially life-threatening
illness throughout the world, particularly in elderly
patients.1 Currently, it is one of the most common
reasons for an emergency department visit, hospitali-
zation, and death in the United States.2,3 Hospital
admissions due to CAP have increased 34% over the
last decade.4 It is also the most frequent cause of
community-acquired infections among patients
admitted to intensive care units.5 Respiratory tract
infections caused by multidrug-resistant Streptococcus
pneumoniae strains, the most common CAP pathogen,
are becoming more frequent.6–8 Therefore, it is
necessary to seek an optimal therapeutic regimen that
safely and effectively controls the infection and
minimizes the risk of drug resistance development.
In the guidelines for CAP released by the Infectious
Diseases Society of America and the American
Thoracic Society (2007),9 levofloxacin, gemifloxacin,
and moxifloxacin were reported to be equally effective
*These authors contributed equally to this work.
Correspondence to: R. Wang, Center of Medicine Clinical Research,
General Hospital of Chinese People’s Liberation Army, 28 Fuxing Road,
Beijing, China. Email: wangr301vip@163.com
lactams and macrolides. The fourth generation of
fluoroquinolones, with enhanced activity against S.
pneumoniae and atypical pathogens, was introduc-
ed into the treatment of CAP patients. However,
fluoroquinolones were associated with adverse events
(AEs) in special patient populations including the
elderly, those with hepatic, renal, or glycemic dis-
orders, and those at risk for cardiovascular events.10
Moxifloxacin (Avelox; Bayer AG, Wuppertal, Ger-
many), an 8-methoxyquinolone, has potent in vitro
activity against both typical Gram-negative and
Gram-positive aerobes and atypical pathogens com-
monly associated with severe CAP.11,12 More than 100
million patients worldwide have received moxiflox-
acin, since it was approved by Germany in 1999 and
many randomized controlled clinical trials have been
published in recent years. However, whether moxi-
floxacin results in a better clinical outcome for mild-to-
moderate and severe CAP remains unclear. Here, we
performed a meta-analysis to compare the efficacy and
safety of moxifloxacin with other antimicrobial agents
used for treatment of CAP to evaluate whether it
possesses more advantages or disadvantages in treat-
ment of CAP patients.

ß 2012 Edizioni Scientifiche per l’Informazione su Farmaci e Terapia

DOI 10.1179/1973947812Y.0000000028 Journal of Chemotherapy 2012 VOL . 24 NO . 5 257
Yuan et al. Treatment of CAP with moxifloxacin
Methods
Search strategy
The study was performed with a prespecified search
strategy and study eligibility criteria. We searched
PubMed, EMBASE, and Web of Science up to
December 2011, and the Cochrane Central Register
of Controlled Trials (Cochrane Library Issue 1, 2012)
using the search terms ‘moxifloxacin’, ‘Avelox’,
‘pneumonia’, ‘community-acquired pneumonia’, and
‘CAP’ in the title, abstract, or keywords. We also
searched reference lists of retrieved articles for other
relevant papers. The search was limited to rando-
mized controlled trials. All reference lists from the
relevant articles and reviews were searched for
additional eligible studies. Experts in the field were
also consulted. The articles that were not available to
us were requested from the authors.
Study selection
Three reviewers (XY, BL, and CS) independently
searched the literature and examined the identified
relevant trials for data on efficacy and safety.
Potentially relevant studies were selected according
to title and abstract review of all initially identified
articles. All studies that fulfilled the following inclu-
sion criteria were included in the meta-analysis: (1)
comparison of the clinical efficacy of moxifloxacin and
other antibiotics in patients with CAP; (2) randomized
allocation of patients to moxifloxacin group or the
controlled group; (3) availability of results in terms
of cure or clinical success at a follow-up visit dur-
ing which cure or improvement was assessed; and (4)
trials with blinded or unblinded design were included.
Experimental trials and trials focused on pharmaco-
kinetic or pharmacodynamic variables were excluded.
We also excluded trials in which moxifloxacin was not
the primary therapeutic drug.
Data extraction
Three reviewers (XY, BL, and CS) extracted the data
from included trials independently. Any disagreement
was resolved by consensus or by another reviewer.
When necessary, the authors of the trials were contacted
for clarification and further information on their trials.
Data extracted from the relevant articles included year
of publication, type of study, the randomization
procedure, number of participants [intention to treat
(ITT), valid-per-protocol (PP) population, and micro-
biologically valid population], intervention (antimicro-
bial agents and doses), clinical and microbiological
outcomes, total AE, drug-related AE, and mortality.
The ITT analysis included those patients that were
randomized and received at least 1 dose of the study
drug. The clinically evaluable population was com-
prised of patients that fulfilled all inclusion and
exclusion criteria in the individual randomized control
trials (RCTs), had complete follow-up, and for whom
258 Journal of Chemotherapy 2012 VOL . 24 NO .
data on treatment outcomes were available but not
indeterminate. The microbiologically evaluable popula-
tion was a subset of the clinically evaluable population
that also had microbiological evaluation data.
Qualitative assessment
Evaluation of the methodological quality of the RCTs
included in the meta-analysis was performed indepen-
dently by two reviewers (XY and CS) using the Jadad
scoring system as follows: a quality review of each
RCT was performed by examining details of rando-
mization, generation of random numbers, details of
the double-blinding procedure, information on with-
drawals, and concealment of allocation.13 One point
was awarded for the specification of each of the above
criteria; the maximum score for a study was 5. A high
quality RCT score was more than four points, while a
low quality RCT score was 2 or fewer points, accord-
ing to the reported methodology.14
Definitions of CAP
We included trials that defined pneumonia according
to the following criteria: a baseline chest radiograph
that demonstrated new or progressive infiltrates, or
consolidation with or without effusion, and any one
of the following signs and symptoms: fever (>38uC),
cough, new or worsened purulent sputum produc-
tion, rales or signs of pulmonary consolidation or
both, dyspnea or hypoxemia, or both.9
Definition of outcomes
Our primary outcome was treatment success at the
test-of-cure (TOC) visit. The secondary outcomes
included the bacteriological response, probable or
possible drug-related AEs, and all-cause mortality for
this meta-analysis. Treatment success (‘cure’, defined
as resolution of all symptoms and signs of infection;
‘improvement’, defined as resolution of two or more
of the baseline symptoms or signs of infection) was
assessed both in the PP and ITT populations at the
TOC visit. Clinically assessed patients in the indivi-
dual RCTs who had an indeterminate clinical out-
come (i.e., their condition could not be assessed as
improvement or failure, or follow-up data were
inadequate) at the TOC visit were deemed unassessed
for the analysis of treatment success. Furthermore,
we also assessed total AEs in ITT populations to
determine differences between the groups.
Data analysis and statistical methods
Statistical analyses were performed using RevMan
5.0. Dichotomous data were analyzed by calculating
the odds ratio (OR) for each trial with 95%
confidence intervals (CIs). Where appropriate, we
conducted meta-analyses of the included studies
provided there was no significant heterogeneity. We
assessed heterogeneity between trials using the Chi-
squared and I2 tests. In the analysis of heterogeneity,
a P value lower than 0.01 was defined as statistically
5

Figure 1 Retrieval and selection of randomized controlled
trials included in the meta-analysis of moxifloxacin for the
treatment of CAP.
significant. Mild heterogeneity might account for less
than 25% of the variability in I2, and notable
heterogeneity substantially more than 50%. We assess-
ed publication bias using the funnel plot method and
Egger’s test.15 Pooled OR and 95% CI for all pri-
mary and secondary outcomes were calculated using
both the Mantel–Haenszel fixed effects and the
DerSimonian–Laird random effects models. For all
analyses, the results from the fixed effects model
(FEM) were presented only when there was no
heterogeneity between trials; otherwise, the results
from the random effects model were presented. The
difference in the OR of the outcome using moxiflox-
acin for CAP compared with other antimicrobial
agents was statistically analyzed.
Results
Description of clinical trials
The flow diagram in Fig. 1 shows the detailed screen-
ing and selection process applied before including
trials in the meta-analysis. Fourteen RCTs containing
6923 patients were included in our meta-analysis. Nine
RCTs compared moxifloxacin with beta-lactam-based
therapies,16–24 Three RCTs compared moxifloxacin
with levofloxacin,25–27 and two RCTs compared
moxifloxacin with macrolides.28,29 The duration of
moxifloxacin trials was 7–14 days17,19,20,21,23–25,27 or
10 days.16,18,22,26,28,29 All trials (except Ref. 29) used a
regimen of intravenous (IV) or per os (PO) moxiflox-
acin at a dose of 400 mg, every day (QD), while
Hoeffken29 assessed different dosages of moxifloxacin
(200 or 400 mg) once daily IV or PO; only the data
pertaining to 400 mg dosage of moxifloxacin were
extracted and compared. The 14 articles included were
evaluated by methodological quality scores and were
considered high quality studies with the scores ranging
from 3 to 5. We examined the funnel plot (standard
error of log OR plotted against ORs) to estimate
publication bias, showing a symmetric inverse funnel
distribution. The main characteristics of the 14 RCTs
(type of study design, characteristics of the included
Yuan et al. Treatment of CAP with moxifloxacin
population, antimicrobial agents and doses used,
number of enrolled patients and ITT patients, and
Jadad score) are presented in Table 1.
Efficacy
The pooled data of moxifloxacin compared with other
antimicrobial agents for clinical treatment success are
shown in Fig. 2. Data regarding treatment success in
clinically evaluable populations at the TOC visit (the
primary outcome) were available for all 14 trials. The
total clinical treatment success of the moxifloxacin
group was similar to that of the comparator group in
the clinically evaluable population at the TOC visit
(4468 patients; FEM; OR: 1.12; 95% CI: 0.91–1.36)
(Fig. 2A). Regarding the ITT population, there were
nine trials providing data on treatment success at the
TOC visit and no significant difference was found
between the moxifloxacin group and the whole
comparator group (3480 patients; FEM; OR: 1.06;
95% CI: 0.89–1.25) (Fig. 2B). There was also no
significant difference between moxifloxacin and con-
trols (P.0.05 for all) within the three subgroups with
different antibiotics (moxifloxacin vs. macrolides, moxi-
floxacin vs. beta-lactam-based therapy, and moxi-
floxacin vs. levofloxacin) (Fig. 2A (2.1.1, 2.1.2, and
2.1.3)).
Seven trials provided data about treatment success
in patients with severe CAP. The effectiveness of both
antibiotic regimens was high (moxifloxacin 86.0%,
comparator antibiotics 83.1%) and there was no
difference in treatment success between the two groups
(952 patients; FEM; OR: 1.28; 95% CI: 0.89–1.83). In
the analysis that included only trials concerning severe
CAP treatment with combination regimens, treatment
success was not different between the moxifloxacin
group and comparator regimens (738 patients; FEM;
OR: 1.29; 95% CI: 0.85–1.97) (data not shown).
Bacteriologic outcomes
The bacteriological responses were recorded in the
RCTs except for Refs. 19 and 21. The microbiological
outcomes for different bacteria from the randomized
controlled trials in the meta-analysis are presented in
Table 2. In the microbiologically valid population,
bacteriologic success (i.e. eradication or presumed
eradication of the causal pathogen) at the TOC visit
was higher in the moxifloxacin group than in the
comparator group (1126 patients; FEM; OR: 1.47;
95% CI: 1.04–2.08) (Fig. 3), which showed that
moxifloxacin may be more effective at eradicating
bacteria. However, it is of interest to investigate the
subgroups where the results were different. No
statistically significant differences were found between
the moxifloxacin and comparator groups in the
moxifloxacin vs. macrolides (289 patients; FEM; OR:
1.49; 95% CI: 0.66–3.37) (Fig. 3 (3.1.1)) or the moxi-
floxacin vs. levofloxacin (293 patients; FEM; OR: 1.12;
Journal of Chemotherapy 2012 VOL . 24 NO . 5 259
260
Table 1 Main characteristics and Jadad score of RCTs included in the meta-analysis
Yuan et al.

Drug regimens
Enrolled Intention to Jadad
Study Type of study Included population Moxifloxacin Compared regimens population treat score

Fogarty28 Prospective, multicenter, Outpatients >18 years old with mild- Oral moxifloxacin 400 mg QD Oral clarithromycin 500 mg BID 474 237 vs. 236 4
(1999) double-blind, RCT to-moderate CAP
Petitpretz16 Prospective, multinational, Patients >18 years old with mild-to- Oral moxifloxacin 400 mg QD Oral amoxicillin 1000 mg TID 411 200 vs. 208 4

Journal of Chemotherapy
(2001) multicenter, double-blind, moderate CAP of suspected
RCT pneumococcal origin
File25 Prospective, multinational, Subjects >18 years old with mild-to- Sequential IV/PO moxifloxacin Sequential IV/PO levofloxacin 516 249 vs. 258 5

2012
(2001) multicenter, double-blind, moderate or severe CAP requiring IV 400 mg QD 500 mg QD
RCT therapy
Treatment of CAP with moxifloxacin

Hoeffken29 Prospective, double-blind, Outpatients >18 years old with mild- Oral moxifloxacin 200 mg or Oral clarithromycin 500 mg BID 678 229 (200 mg), 4

VOL .
(2001) RCT to-moderate CAP 400 mg QD 224 (400 mg)

24
vs. 222
Finch17 Multinational, multicenter, Patients >18 years old with Sequential IV/PO moxifloxacin IV co-amoxiclav 1.2 g TID followed 628 301 vs. 321 4
(2002) open-label, RCT radiological evidence of CAP 400 mg QD by oral co-amoxiclav 625 mg TID

NO .
requiring initial parenteral therapy, with or without clarithromycin 500

5
half with severe CAP mg BID
Jardim18 Prospective, multinational, Patients >18 years old with Oral moxifloxacin 400 mg QD oral amoxicillin 500 mg TID 84 39 vs. 45 4
(2003) multicenter, double-blind, mild-to-moderate CAP of
RCT suspected pneumococcal origin
Torres19 Double-blind, RCT Patients >18 years old with mild-to- Oral moxifloxacin 400 mg QD Oral amoxicillin 1 g TID, clarithromycin 564 233 vs. 244 4
(2003) moderate or severe CAP 500 mg BID, or the association of both
regimens
Katz20 Prospective, multi-center, Patients >18 years old with mild- Sequential IV to PO moxifloxacin IV ceftriaxone 2 g/day followed by PO 1340 167 vs. 168 4
(2004) open-label, RCT to-moderate or severe 400 mg QD cefuroxime 500 mg BID
CAP requiring IV therapy
Welte21 Prospective, multinational, Hospital-admitted patients aged > IV/PO moxifloxacin 400 mg QD IV 2 g ceftriaxone with or without 1 g 397 200 vs. 197 4
(2005) multicenter, open-label, 18 years with mild-to- erythromycin QD
RCT moderate or severe CAP requiring
initial parenteral therapy
Portier22 Prospective, multicenter, Hospitalized patients >18 years old Oral moxifloxacin 400 mg QD combination of amoxicillin-clavulanate 349 171 vs. 175 3
(2005) open-label, RCT with non-severe CAP 1000/125 mg
TID and roxithromycin 150 mg BID
Kobayashi26 Double-blind, RCT Patients aged 20–79 years with CAP Oral moxifloxacin 400 mg QD Oral levofloxacin 100 mg TID 306 149 vs. 153 4
(2005)
Xu23 (2006) Parallel, RCT Patients >18 years old with IV moxifloxacin 400 mg QD IV 2 g cefoperazone TID with IV 0.5 g 40 20 vs. 20 3
radiological evidence of mild-to azithromycin QD
-moderate CAP
Anzueto27 Prospective, double-blind, Hospitalized elderly patients >65 Sequential IV/PO moxifloxacin Sequential IV/PO levofloxacin 401 195 vs. 199 4
(2006) double-dummy, RCT years with clinical signs and symptoms 400 mg QD 500 mg/day
of mild-to-moderate or severe CAP,
radiologically confirmed evidence of
a new and/or progressive infiltrate(s) and a
requirement for initial parenteral therapy
Torres24 Prospective, multicenter, Patients aged >18 years with CAP PSI Sequential IV/PO moxifloxacin IV ceftriaxone 2 g/day plus sequential 738 368 vs. 365 4
(2008) double-blind, RCT class III–V who required hospitalization 400 mg QD IV/PO levofloxacin 500 mg TID
and initial IV antibiotic therapy

Note: RCT: randomized controlled trial; CAP: community-acquired pneumonia; IV: intravenous; QD: daily; PO: per os; BID: twice daily; TID: three times daily.
 Yuan et al. Treatment of CAP with moxifloxacin

Figure 2 Meta-analysis of clinical treatment success comparing moxifloxacin with compared regimens for CAP treatment. (A)
Clinical treatment success analysis based upon the clinically evaluable population at the TOC visit. (B) Clinical treatment
success analysis based upon the ITT population at the TOC visit.

95% CI: 0.57–2.19) (Fig. 3 (3.1.3)) subgroups. indicated moxifloxacin was more effective at eradicat-
However, there was strong evidence in the moxiflox- ing bacteria (544 patients; FEM; OR: 1.67; 95% CI:
acin vs. beta-lactam-based therapy subgroup that 1.04–2.68) (Fig. 3 (3.1.2)).

Journal of Chemotherapy 2012 VOL . 24 NO . 5 261

Yuan et al. Treatment of CAP with moxifloxacin

Adverse effects

5/5 (100)
Control
pneumoniae

1/2 (50)
The most common drug-related AEs in the moxi-
Klebsiella

—
—
0

—
—
floxacin group were gastrointestinal disturbances
including diarrhea, vomiting, and nausea (in descend-

6/6 (100)

1/2 (50)
1/2 (50)

1/2 (50)
MOF
ing order of frequency). These were generally of mild

—
—
—
—
—

—
—
—
—
to moderate severity.
Data on total AEs in the ITT populations were
6/6 (100) 2/2 (100)

2/2 (100)

5/5 (100)
Control

reported for nine trials. There was no difference in

catarrhalis
Moraxella

—
—
—
—
—

—
—
—
—
total AEs between the moxifloxacin group and the
control group (3684 patients; FEM; OR: 1.01; 95% CI:
4/5 (80)

4/5 (80)
0.88–1.15) (Fig. 4A). In the subgroup analysis, there
MOF

0/1 (0)

were no significant differences in the moxifloxacin vs.

—

—
—
—
—
—

—
—
—
—

macrolides or the moxifloxacin vs. beta-lactam-based

therapy subgroups, However, the rate of treatment-
1/3 (33.3)

6/7 (85.7)
5/5 (100)

3/3 (100)
Control
Staphylococcus

emergent AEs due to any cause was significantly

—

—
—
—
—
—

—
—
—
higher in the moxifloxacin-treated patients (P50.03)
than in the levofloxacin group (Fig. 4A (4.1.3)), but
aureus

the rates of drug-related AEs were similar for both the

22/23 (96) 14/16 (87.5) 23/24 (96) 20/20 (100) 47/51 (92) 48/49 (98) 5/5 (100)

2/2 (100)

4/5 (80) 2/2 (100)

2/2 (100)
MOF

treatments (Fig. 4B (4.2.3)). Data on drug-related AEs

in the ITT populations were reported for 12 RCTs and
—

—
—
—
—
—

—
—
—

there was no difference between the treatment groups

8/8 (100)
Control

(4867 patients; random effects model; OR: 1.02; 95%

—

—
—
—
—
—
—
—
—
—
Chlamydia sp.

CI: 0.83–1.26) in total analysis and subgroups analysis

(Fig. 4B).
3/3 (100)
9/10 (90) 13/13 (100) 10/11 (91)

Mortality
Table 2 Microbiological outcomes for bacteria from the randomized controlled trials in the meta-analysis

MOF

—
—
—
—
—
—
—
—
—

All-cause mortality was available in 12 trials. There

was no significant difference in mortality between
moxifloxacin and the compared regimen (4964
8/9 (88.9) 13/13 (100) 11/17 (94.1)
Control

patients; FEM; OR: 1.02; 95% CI: 0.75–1.37) (Fig. 5).

Mycoplasma sp.

—
—
—
—
—
—
—
—
—

Sensitivity analysis
In the analysis of only blinded trials, there were no
differences in treatment success rates (2701 patients;
MOF

—
—
—
—
—
—
—
—
—

FEM; OR: 0.95; 95% CI: 0.72–1.25), biological

response rates (723 patients; FEM; OR: 1.16; 95%
CI: 0.74–1.83), AE rates (3492 patients; FEM; OR:
18/21 (85.7) 14/14 (100) 12/14 (85.7)
9/9 (100) 15/18 (83)
11/13 (85) 14/16 (88)
9/9 (100) 7/10 (70)
Control

1.10: 95% CI: 0.96–1.26), and mortality rates (2561

Haemophilus

—
—
—
—
—

—
—
—

patients; FEM; OR: 1.30; 95% CI: 0.86–1.97) between

influenzae

the moxifloxacin group and the comparator regimens.

13/13 (100)
17/22 (77.3) 11/11 (100)

Discussion
—
—
—
—
—

—
—
—

Two earlier pooled analyses performed by Lode et al.30

MOF

and Hoeffken et al.31 provided evidence that moxi-

(91.7)

16/18 (88.9)

38/45 (84.4)

floxacin was comparable to other recommended

(95)
(85)
(88)
Streptococcus

antimicrobial regimens (standard fluoroquinolones,

Control

—
—
—
—

—
—
pneumoniae

18/19
39/46
29/33
11/12

combinations of beta-lactams and macrolides) for the

treatment of CAP. However, since the two pooled
19/21 (90.5)

19/24 (79.2)

27/32 (84.4)
17/17 (100)

18/18 (100)

14/14 (100)

analyses included only two trials separately, more

43/48 (90)
31/35 (89)
19/20 (95)
MOF

RCTs are needed to support this hypothesis. An et al.32

—
—
—
—

—
—

performed a meta-analysis of moxifloxacin monother-

Note: MOF: moxifloxacin.

apy versus beta-lactam-based standard therapy for

Pathogen

CAP, which were included in seven RCTs and found

Kobayashi26 (2005)
Petitpretz16 (2001)

Hoeffken29 (2001)

Anzueto27 (2006)
Fogarty28 (1999)

that moxifloxacin can not only be used as effectively

Jardim18 (2003)

Portier22 (2005)
Torres19 (2003)

Torres24 (2008)
Welte21 (2005)
Finch17 (2002)

Katz20 (2004)

and safely as beta-lactam-based standard therapy, but

File25 (2001)

Xu23 (2006)
Eradication

also possesses a favourable pathogen eradication rate.

study

To compare the efficacy and safety of moxifloxacin

and other recommended antimicrobial regimens

262 Journal of Chemotherapy 2012 VOL . 24 NO . 5


Figure 3 Meta-analysis of microbiological treatment success comparing moxifloxacin to comparative regimens for CAP
treatment based on microbiologically evaluable populations at the TOC visit.
(standard fluoroquinolones, beta-lactam6macrolides,
and macrolides alone9), particularly in patients with
severe CAP, the analysis included 14 RCTs (including
the seven RCTs analyzed by An et al.).32
Vardakas et al.33 reported a meta-analysis of
respiratory fluoroquinolones and comparator antibio-
tics for treatment of CAP that suggested the fluor-
oquinolones were associated with a higher success of
treatment for pneumonia with no difference in
mortality compared to the comparator antibiotics.
The major limitation of that meta-analysis was that
there were many open-label trials included and the
results were different when only blinded trials were
compared. The systematic review presented here was
performed on 14 RCTs, most of which were blinded
trials, and has made the most comprehensive meta-
analysis comparing moxifloxacin with other antibiotic
agents, including beta-lactams, macrolides, and other
fluoroquinolones in CAP patients. The results of the
meta-analysis suggest that moxifloxacin was asso-
ciated with similar overall rates of clinical treatment
success, mortality, AEs, and higher microbiological
treatment success rates than the comparator regimens
(Figs. 2–5). Importantly, the meta-analysis found that
moxifloxacin had similar effectiveness as combination
regimens in patients with severe CAP.
Yuan et al. Treatment of CAP with moxifloxacin
Additionally, moxifloxacin treatment was associated
with higher eradication rates in microbiological evalu-
able populations at the TOC visit. The advantage of
moxifloxacin in bacteria eradication was more sig-
nificant when compared with beta-lactams6macro-
lides (Fig. 3 (3.1.2)), but there was no difference when
compared to macrolides and levofloxacin. This result is
similar to the previous study performed by An et al.32
S. pneumoniae was the most frequently isolated
pathogen in these RCTs, except that of Fogarty et al.28
which found that an atypical pathogen was isolated
most frequently. The resistance of S. pneumoniae to
macrolides and beta-lactams has increased in recent
years, which may explain why moxifloxacin demon-
strates higher bacteria eradication than beta-lactam-
based therapy.
The safety results of our meta-analysis have shown
moxifloxacin to be generally well-tolerated and safe
with overall AE frequencies comparable to that of the
comparator regimens of beta-lactams, macrolides,
and other fluoroquinolones. Similar to the compara-
tors, moxifloxacin has demonstrated a low propensity
to cause central nervous system reactions, no
potential for phototoxicity, and minimal, but clini-
cally insignificant, increases in the heart rate-cor-
rected QT interval. Mortality was also similar
Journal of Chemotherapy 2012 VOL . 24 NO . 5 263
Yuan et al. Treatment of CAP with moxifloxacin

Figure 4 Meta-analysis of AEs comparing moxifloxacin with compared regimens for CAP treatment during the treatment and
the post-treatment period. (A) The analysis of total AEs based upon the ITT population. (B) The analysis of drug-related AEs
based upon the ITT population.

264 Journal of Chemotherapy 2012 VOL . 24 NO . 5


Figure 5 Meta-analysis of mortality comparing moxifloxacin to comparative regimens for CAP treatment during the treatment
and the post-treatment period based upon the ITT population.
between the comparator regimens. This result is
similar to the previous study performed by van
Bambeke et al.34
A prospective, double-blind, randomized trial
performed by Morganroth et al.35 focused on the
cardiac rhythm safety of moxifloxacin compared to
levofloxacin. Approximately 400 elderly patients
participated, of whom two thirds were considered
very elderly (.75 years old), and nearly half were
female. A large majority of patients had significant
comorbid cardiac conditions (72% for moxifloxacin
and 76% for levofloxacin) in addition to the current
episode of CAP for which they received IV anti-
microbial therapy. The study found that the incidence
of cardiac events, primarily atrial fibrillation and
non-sustained ventricular tachycardia, during the
treatment of elderly patients hospitalized with CAP,
was quite high. However, there were no significant
differences between moxifloxacin (a drug known to
increase corrected QT duration) and levofloxacin.
As moxifloxacin is not metabolized via the
cytochrome P450 system, the potential for interac-
tions with comedications is low, and except for the
typical absorption class interaction of quinolones
with antacids and minerals, no other clinically
relevant interactions have been demonstrated. Dose
Yuan et al. Treatment of CAP with moxifloxacin
adjustments for renal or hepatic insufficiency are not
required, as moxifloxacin is excreted in a balanced
fashion via renal, hepato/biliary, and metabolic
pathways.36,37 The convenient once daily dosing
regimen of moxifloxacin may offer an advantage in
terms of improved patient compliance and thus a
reduction in the likelihood of resistance selection. In
vitro and in vivo experiments have demonstrated that
moxifloxacin has a low propensity for selecting
resistant organisms, with a spontaneous mutation
frequency towards moxifloxacin in S. pneumoniae of
1029, two orders of magnitude lower than other
quinolones.38
The findings of the present study must be viewed in
the context of potential limitations. First, five of the
included trials were non-blind trials. This may have
introduced bias into the reported outcomes of
effectiveness. Additionally, the biological response
bias analysis was different when open-label trials
were included in the analysis. Therefore, more RCT
trials are needed to confirm the higher pathogen
eradiation rate of moxifloxacin compared to other
antibiotics. Second, some included trials did not
include detailed AEs. Although we endeavoured to
extract data regarding different AEs, this may have
an influence on the safety results. Third, one RCT
Journal of Chemotherapy 2012 VOL . 24 NO . 5 265
Yuan et al. Treatment of CAP with moxifloxacin
assessed the efficacy and safety in the elderly21 and
two RCTs only included patients with infections
caused by S. pneumoniae.16,18 All of these differences
in the included trials may generate bias in the
assessment of outcomes.
Conclusions
Despite its limitations, this represents the largest meta-
analysis of studies of moxifloxacin for the treatment of
CAP to date. We found that moxifloxacin is associated
with clinical and survival outcomes that are on par
with comparative antimicrobial regimens in CAP
patients. However, moxifloxacin appears to have
superior microbiological eradication efficacy com-
pared to beta-lactam-based therapy. Also, the once
daily dosing of moxifloxacin may be a useful
alternative to combination and/or multidosed anti-
biotic regimens. However, since there are few trials
stratifying the patients and severity, differences may
exist in mild to severe patients. More well-designed,
randomized, and controlled trials are needed to better
understand these differences.
Acknowledgements
The current authors are indebted to the authors of
the primary studies.
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