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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
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
Figure 1 Retrieval and selection of randomized controlled
trials included in the meta-analysis of moxifloxacin for the
the clinically evaluable population at the TOC visit
treatment of CAP. (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
significant. Mild heterogeneity might account for less TOC visit and no significant difference was found
than 25% of the variability in I2, and notable between the moxifloxacin group and the whole
heterogeneity substantially more than 50%. We assess- comparator group (3480 patients; FEM; OR: 1.06;
ed publication bias using the funnel plot method and 95% CI: 0.89–1.25) (Fig. 2B). There was also no
Egger’s test.15 Pooled OR and 95% CI for all pri- significant difference between moxifloxacin and con-
mary and secondary outcomes were calculated using trols (P.0.05 for all) within the three subgroups with
both the Mantel–Haenszel fixed effects and the different antibiotics (moxifloxacin vs. macrolides, moxi-
DerSimonian–Laird random effects models. For all floxacin vs. beta-lactam-based therapy, and moxi-
analyses, the results from the fixed effects model floxacin vs. levofloxacin) (Fig. 2A (2.1.1, 2.1.2, and
(FEM) were presented only when there was no 2.1.3)).
heterogeneity between trials; otherwise, the results Seven trials provided data about treatment success
from the random effects model were presented. The in patients with severe CAP. The effectiveness of both
difference in the OR of the outcome using moxiflox- antibiotic regimens was high (moxifloxacin 86.0%,
acin for CAP compared with other antimicrobial comparator antibiotics 83.1%) and there was no
agents was statistically analyzed. difference in treatment success between the two groups
(952 patients; FEM; OR: 1.28; 95% CI: 0.89–1.83). In
Results the analysis that included only trials concerning severe
Description of clinical trials CAP treatment with combination regimens, treatment
The flow diagram in Fig. 1 shows the detailed screen- success was not different between the moxifloxacin
ing and selection process applied before including group and comparator regimens (738 patients; FEM;
trials in the meta-analysis. Fourteen RCTs containing OR: 1.29; 95% CI: 0.85–1.97) (data not shown).
6923 patients were included in our meta-analysis. Nine
RCTs compared moxifloxacin with beta-lactam-based Bacteriologic outcomes
therapies,16–24 Three RCTs compared moxifloxacin The bacteriological responses were recorded in the
with levofloxacin,25–27 and two RCTs compared RCTs except for Refs. 19 and 21. The microbiological
moxifloxacin with macrolides.28,29 The duration of outcomes for different bacteria from the randomized
moxifloxacin trials was 7–14 days17,19,20,21,23–25,27 or controlled trials in the meta-analysis are presented in
10 days.16,18,22,26,28,29 All trials (except Ref. 29) used a Table 2. In the microbiologically valid population,
regimen of intravenous (IV) or per os (PO) moxiflox- bacteriologic success (i.e. eradication or presumed
acin at a dose of 400 mg, every day (QD), while eradication of the causal pathogen) at the TOC visit
Hoeffken29 assessed different dosages of moxifloxacin was higher in the moxifloxacin group than in the
(200 or 400 mg) once daily IV or PO; only the data comparator group (1126 patients; FEM; OR: 1.47;
pertaining to 400 mg dosage of moxifloxacin were 95% CI: 1.04–2.08) (Fig. 3), which showed that
extracted and compared. The 14 articles included were moxifloxacin may be more effective at eradicating
evaluated by methodological quality scores and were bacteria. However, it is of interest to investigate the
considered high quality studies with the scores ranging subgroups where the results were different. No
from 3 to 5. We examined the funnel plot (standard statistically significant differences were found between
error of log OR plotted against ORs) to estimate the moxifloxacin and comparator groups in the
publication bias, showing a symmetric inverse funnel moxifloxacin vs. macrolides (289 patients; FEM; OR:
distribution. The main characteristics of the 14 RCTs 1.49; 95% CI: 0.66–3.37) (Fig. 3 (3.1.1)) or the moxi-
(type of study design, characteristics of the included floxacin vs. levofloxacin (293 patients; FEM; OR: 1.12;
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)).
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
—
—
—
—
—
—
—
—
—
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)
—
—
—
—
—
—
—
—
—
6/7 (85.7)
5/5 (100)
3/3 (100)
Control
Staphylococcus
—
—
—
—
—
—
—
—
higher in the moxifloxacin-treated patients (P50.03)
than in the levofloxacin group (Fig. 4A (4.1.3)), but
aureus
2/2 (100)
2/2 (100)
MOF
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Chlamydia sp.
Mortality
Table 2 Microbiological outcomes for bacteria from the randomized controlled trials in the meta-analysis
MOF
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Sensitivity analysis
In the analysis of only blinded trials, there were no
differences in treatment success rates (2701 patients;
MOF
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Discussion
—
—
—
—
—
—
—
—
16/18 (88.9)
38/45 (84.4)
—
—
—
—
—
—
pneumoniae
18/19
39/46
29/33
11/12
19/24 (79.2)
27/32 (84.4)
17/17 (100)
18/18 (100)
14/14 (100)
—
—
Hoeffken29 (2001)
Anzueto27 (2006)
Fogarty28 (1999)
Portier22 (2005)
Torres19 (2003)
Torres24 (2008)
Welte21 (2005)
Finch17 (2002)
Katz20 (2004)
Xu23 (2006)
Eradication
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.
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.
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 adjustments for renal or hepatic insufficiency are not
similar to the previous study performed by van required, as moxifloxacin is excreted in a balanced
Bambeke et al.34 fashion via renal, hepato/biliary, and metabolic
A prospective, double-blind, randomized trial pathways.36,37 The convenient once daily dosing
performed by Morganroth et al.35 focused on the regimen of moxifloxacin may offer an advantage in
cardiac rhythm safety of moxifloxacin compared to terms of improved patient compliance and thus a
levofloxacin. Approximately 400 elderly patients reduction in the likelihood of resistance selection. In
participated, of whom two thirds were considered vitro and in vivo experiments have demonstrated that
very elderly (.75 years old), and nearly half were moxifloxacin has a low propensity for selecting
female. A large majority of patients had significant resistant organisms, with a spontaneous mutation
comorbid cardiac conditions (72% for moxifloxacin frequency towards moxifloxacin in S. pneumoniae of
and 76% for levofloxacin) in addition to the current 1029, two orders of magnitude lower than other
episode of CAP for which they received IV anti- quinolones.38
microbial therapy. The study found that the incidence The findings of the present study must be viewed in
of cardiac events, primarily atrial fibrillation and the context of potential limitations. First, five of the
non-sustained ventricular tachycardia, during the included trials were non-blind trials. This may have
treatment of elderly patients hospitalized with CAP, introduced bias into the reported outcomes of
was quite high. However, there were no significant effectiveness. Additionally, the biological response
differences between moxifloxacin (a drug known to bias analysis was different when open-label trials
increase corrected QT duration) and levofloxacin. were included in the analysis. Therefore, more RCT
As moxifloxacin is not metabolized via the trials are needed to confirm the higher pathogen
cytochrome P450 system, the potential for interac- eradiation rate of moxifloxacin compared to other
tions with comedications is low, and except for the antibiotics. Second, some included trials did not
typical absorption class interaction of quinolones include detailed AEs. Although we endeavoured to
with antacids and minerals, no other clinically extract data regarding different AEs, this may have
relevant interactions have been demonstrated. Dose an influence on the safety results. Third, one RCT
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Moxifloxacin monotherapy versus beta-lactam-based standard Poster presented at First International Moxifloxacin
therapy for community-acquired pneumonia: a meta-analysis of Symposium; 1999; Berlin, Germany.