criticism of the article "Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia The LEAP 2 Randomized Clinical Trial"

1. Presented by: Farah el Soheil
Instructor: Dr. Razan Mhanna
1

2. Lebanese International University
School of Pharmacy
Advanced Pharmacy Practice Experience
Infectious Diseases Department
Oral Lefamulin vs Moxifloxacin for Early
Clinical Response Among Adults With
Community-Acquired Bacterial Pneumonia The
LEAP 2 Randomized Clinical Trial
2
October 30, 2019

3.  General Overview
 Journal Club
 Journal
 Title
 Authors
 Abstract
 Introduction
 Method
 Results
 Discussion
 Conclusion
 Reference Evaluation
 Overall Evaluation
 Related Study
Outline
3

4. What’s CAP
4
• Refers to an acute infection of the pulmonary parenchyma
acquired outside of a health care setting
• The most common infectious cause of death
• The second most common cause of hospitalization
Community-acquired pneumonia (CAP)

5. Other Types of Pneumonia
5
• HAP refers to pneumonia acquired ≥48 hours after hospital
admission
• VAP refers to pneumonia acquired ≥48 hours after endotracheal
intubation
Nosocomial pneumonia (Acquired in hospital settings)
• Acquired in healthcare facilities (eg, nursing homes, hemodialysis
centers)
• Acquired after recent hospitalization
• At risk for infection with multidrug-resistant pathogens
Health care-associated pneumonia (HCAP; no longer used)

6. Clinical Presentation of CAP
6
Mild pneumonia
characterized by fever and
productive cough
Severe pneumonia
characterized by respiratory
distress and sepsis

7. Risk Factors
7
Older age – The risk of CAP rises with age ( three times higher than the general
population)
Chronic comorbidities mostly COPD bronchiectasis, asthma, chronic heart
disease and immunocompromising conditions
Viral respiratory tract infection predispose to secondary bacterial pneumonia
Impaired airway protection – Conditions that increase risk of macroaspiration of
stomach contents and/or microaspiration of upper airway secretions predispose to
CAP, such as alteration in consciousness or dysphagia
Smoking and alcohol overuse
Other lifestyle factors include crowded living conditions

8. Common Causative Pathogens
8
Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus influenzae
Moraxella catarrhalis
Atypical pathogens Mycoplasma pneumoniae,
Chlamydophila pneumoniae, and Legionella pneumophila

9. Common Causative Pathogens
9
Condition Commonly encountered pathogen(s)
Alcoholism
Streptococcus pneumoniae, oral anaerobes, Klebsiella
pneumoniae, Acinetobacter species, Mycobacterium tuberculosis
COPD and/or smoking
Haemophilus influenzae, Pseudomonas aeruginosa,
Legionella species, S. pneumoniae, Moraxella catarrhalis,
Chlamydia pneumoniae
Aspiration Gram-negative enteric pathogens, oral anaerobes
Lung abscess
CA-MRSA, oral anaerobes, endemic fungal pneumonia, M.
tuberculosis, atypical mycobacteria
Exposure to bat or bird droppings Histoplasma capsulatum
Exposure to birds Chlamydia psittaci (if poultry: avian influenza)
Exposure to rabbits Francisella tularensis
Exposure to farm animals or parturient cats Coxiella burnetti (Q fever)
HIV infection (early) S. pneumoniae, H. influenzae, M. tuberculosis
HIV infection (late)
The pathogens listed for early infection plus Pneumocystis
jirovecii, Cryptococcus, Histoplasma, Aspergillus, atypical
mycobacteria (especially Mycobacterium kansasii), P.
aeruginosa, H. influenzae
Hotel or cruise ship stay in previous two weeks Legionella species
Travel to or residence in southwestern United States Coccidioides species, hantavirus
Travel to or residence in Southeast and East Asia
Burkholderia pseudomallei, avian (H5N1, H7N9) influenza,
SARS coronavirus
Travel to or residence in the Arabian peninsula Middle East respiratory syndrome coronavirus
Influenza active in community Influenza, S. pneumoniae, Staphylococcus aureus, H. influenzae
Cough >2 weeks with whoop or posttussive vomiting Bordetella pertussis
Structural lung disease (eg, bronchiectasis) Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus
Injection drug use S. aureus, anaerobes, M. tuberculosis, S. pneumoniae
Endobronchial obstruction Anaerobes, S. pneumoniae, H. influenzae, S. aureus
Cont’d

10. Specific Pathogens Risk Factors
10
-Recent hospitalization
or antibiotic use
- Underlying structural
lung disease (eg, cystic
fibrosis or advanced
COPD)
- Immunosuppression
-Repeated exacerbations
of COPD requiring
frequent glucocorticoid
and/or antibiotic use
Pseudomonas
- History of MRSA
skin lesions
- Participation in
contact sports
- Injection drug use
- Crowded living
conditions
- Men who have sex
with men
-End-stage renal
disease
-Antimicrobial
therapy in the prior
three months
-Necrotizing or
cavitary pneumonia,
or presence of
empyema
CA-MRSA
- Recent hospitalization
- Recent antibiotic use
(particularly with a
fluoroquinolone) in the
past 3 months
- Immunosuppression
Healthcare Associated
MRSA

11. Risk Factors for CRE Pseudomonas
11
When signs of severe
sepsis or septic shock are
present
Neutropenic patients
with bacteremia
Burn patients (who have
a high incidence of
multidrug-resistant P.
aeruginosa infections)
with serious infections
In other settings where
the incidence of
resistance to the chosen
antibiotic class is high
(eg, >10 to 15 percent)

12. Pulmonary Signs and Symptoms
12
Cough +/-
sputum
production,
fever,
anorexia
tachycardia
& tachypnea
Pleuritic
chest pain &
increased
work of
breathing
Hypoxemia
due to
impairment
of alveolar
gas
exchange

13. Diagnosis
13
Leukocytosis
with a leftward
shift, or
leukopenia
mediated by
the systemic
inflammatory
response
Pulmonary
opacities on
chest radiograph
due to
accumulation of
WBCs and fluid
Chest
radiograph
include lobar
consolidations,
interstitial
infiltrates and/or
cavitation
Physical
examination:
Abnormal
breath sounds,
including
rales/crackles
and rhonchi.
Tactile fremitus,
egophony, and
dullness to
percussion

14. Differential Diagnosis
15
Acute
exacerbations of
COPD
Influenza and
other respiratory
viral infections
Acute bronchitis
Asthma
exacerbation
Febrile illness
and/or sepsis

15. Pneumonia Severity Index
17
I<51
II 51-70
III 71-90
IV 91-130
V>130

16. Severity Scoring
18
Cont’d

17. Treatment (Outpatient)
19

18. Treatment (General Medical Ward)
20
For Hospitalized Patients
on the General Wards
Risk Factors
for Pseudomonas
Primary
Anaphylaxis to
B Lactams
• Anti-pneumococcal
fluoroquinolone
(levofloxacin, moxifloxa
cin, gemifloxacin)
• The combination of a
beta-lactam plus a
macrolide
• Monotherapy
with tigecycline should
be limited to patients
intolerant of both beta-
lactams and
fluoroquinolones
Levofloxacin plus
• Aztreonam
• Aminoglycoside
(gentamicin,
tobramycin,
or amikacin)
Levofloxacin +
Aminoglycoside
Cont’d

19. Treatment (inpatient-ICU)
21
Severe CAP
Requiring ICU
Pseudomonas MRSA
• Beta-lactam
(ceftriaxone,
cefotaxime,
ampicillin-
sulbactam) plus
either
• IV
azithromycin
• Anti-
pneumococcal
fluoroquinolone
• Anti-
pseudomonal
agent
(piperacillin-
tazobactam
, imipenem,
meropenem,
or cefepime)
PLUS
• Anti-
pseudomonal
fluoroquinolone
(ciprofloxacin
or high-dose
levofloxacin)
• Add either
• Vancomycin
• Linezolid
• Clindamycin if
susceptible
• Ceftaroline is not FDA
approved for pneumonia
caused by MRSA
PS: The combination
of vancomycin and piperacillin
tazobactam has been
associated with acute kidney
injury

20. Newly Approved Drugs
22
• FDA approved for the treatment of CAP
• Has activity against common atypical and typical CAP pathogens,
methicillin-resistant S. aureus (MRSA), many gram-negative rods (but
not Pseudomonas spp) and anaerobes
Omadacycline
• Has activity against many respiratory pathogens including MRSA
and Pseudomonas spp
• FDA approved for the treatment of respiratory tract infections
Delafloxacin
• Narrower spectrum, which includes H. influenza and Moraxella
catarrhalis, MRSA, S. pneumoniae, and atypical CAP pathogens
• Its activity against gram-negative pathogens
including Pseudomonas spp is limited
Lefamulin

21. Moxifloxacin (Avalox®)
23
DNA gyrase & topoisomerase
IV inhibitor
Label: Chronic bronchitis,
Intra-abdominal infections,
Rhinosinusitis, Skin
infections
Fluoroquinolones may
exacerbate muscle weakness
in persons with myasthenia
gravis
Community-acquired
pneumonia (CAP) Oral, IV:
400 mg every 24 hours for 5
days
Side effects: Tendinitis and
tendon rupture, peripheral
neuropathy, superinfection
with CDAD ,dysglycemia,
hepatotoxiciy, Aortic
aneurysm and dissection,
and QT prolongation
Off-label: Diabetic foot
infection, menegitis,
Nocardiosis, Pelvic
inflammatory disease,
Surgical prophylaxis,
Tuberculosis

22. Lefamulin (Xenleta®)
24
Pleuromutilin Antibiotic
inhibits 50s through
interactions with
peptidyl transferase
Label: Community-
acquired pneumonia
IV: 150 mg every 12
hours
Oral: 600 mg every 12
hours
For 5 days
Administer ≥1 hour
before a meal or 2 hours
after a meal
Side effects
QT prolongation, super-
infection and GI
disturbance

23. 25
Evaluation of
the Article

24. Evaluation of the Journal
26

25. 27
Since 1883 JAMA is an international peer-reviewed general medical journal
Acceptance rate is 11% of the more than 7,000 major manuscripts it receives
annually
Journal Reach: JAMA is the most widely circulated medical journal in the world
over 20 million annual visits to the journal's website
Language: English
Frequency: 48 times/ year in print/online issues
New articles are published several times a week online
Impact factor 2018: 47.7
Evaluation of the Journal
Cont’d

26. 28
Membership
/partnership
JAMA Network family of journals, which includes 11
specialty journals and JAMA Network Open
International Committee of Medical Journal Editors
African Journal Partnership Project
Malawi Medical Journal
International Congress on Peer Review and Biomedical
Publication
Evaluation of the Journal
Cont’d

27. 29
Evaluation of
the Title

28. Evaluation of the Title
30
 Oral Lefamulin vs Moxifloxacin for Early Clinical
Response Among Adults With Community-Acquired
Bacterial Pneumonia The LEAP 2 Randomized
Clinical Trial
Cont’d

29. Evaluation of the Title
31
 Non conclusive and unbiased
 Brief and clear
Mentions
Intervention group
Comparison group
Outcome of interest
Population of interest
Study design
Cont’d

30. 32
Evaluation of
the Authors

31. Elizabeth Alexander
MD
Weill Cornell Medical
College 1300 York Ave Ste
A421 New York
NY 10065
Evaluation of the Authors
33
Primary Author
 An infectious disease
specialist in New York
 Received her medical degree
from Weill Cornell Medical
College of Cornell
University
 Experience: 11-20 years
Cont’d

32. Jennifer Schranz, MD
Nabriva Therapeutics
US Inc, 1000 Continental
Dr, Ste 600, King of Prussia,
PA 19406
jennifer.schranz@nabriva.com
Evaluation of the Authors
34
Last & Corresponding
Author
 Infectious disease specialist
in Phoenixville,
Pennsylvania
 Received her medical degree
from University of Toronto
Faculty of Medicine since
more than 20 years
 Chief medical officer at
Nabriva Therapeutics
1065 Citations on research gate
Cont’d

33. Evaluation of the Authors
35
 12 reputable authors & experienced in the field
of medicine, however
 Drs Alexander, Spera, Paukner, Gelone, and
Schranz and Ms Goldberg and Mr Wicha are
employees of and own stock in Nabriva
Therapeutics plc
 Statistical analysis:
 Carolyn Sweeney, MPH, is an Associate Director
in the Surveys and Observational Studies group
at RTI-HS
 A clinical pharmacist & a dietitian were
included
 Corresponding author can be contacted
Cont’d

34. 36
Evaluation of
the Funding

35. Evaluation of the Funding
37
Funding :
 The study was funded by Nabriva Inc. the
manufacturer of lefamulin
Cont’d

36. Funding :
 Nabriva was responsible for
 Design & conduct of the study
 Collection and analysis of data
 Preparation and review of manuscript
 However Nabriva Therapeutics didn’t have the
right to veto or suppress publication
Evaluation of the Funding
38
Cont’d

37. 39
Evaluation of
the Abstract

38. Objective :
Evaluation of the Abstract
40
 Mentions :
 Objective
 Population of interest (patients with CABP)
 Doesn’t mention :
 Study design
 Comparison group
Cont’d

39. Evaluation of the Abstract
41
Methods :
Cont’d

40. Evaluation of the Abstract
42
Methods :
Mentions
Study design
Type of blinding &
randomization
Interventions for
both groups
1ry & 2ry end
points & non
inferiority margin
Basic
inclusion/exclusion
criteria
Follow up duration
Total number of
participants
Cont’d

41. Results :
Evaluation of the Abstract
43
Mentions
Baseline characteristics
Results consistent with the study’s
outcome
P values and confidence intervals
Total number of participants
Interventions for each group
Cont’d

42. Evaluation of the Abstract
44
Conclusion :
 Clear and concise
 Doesn’t offer a base for future clinical trials
Cont’d

43. 45
Evaluation of
the Introduction

44. Evaluation of the Introduction
46
Previous Studies, Rationale & Objective:
IV lefamulin
vs
moxifloxacin
Non
inferiority
results
Rationale to
conduct leap
2 trial
Cont’d
Objective Rationale Previous studies

45. Evaluation of the Introduction
47
Overall Evaluation:
 Disease and treatment overview
 Mentions the results of previous studies
 Mentions the rationale and objective
respectively
 Based on facts
 Lacks the hypothesis
Cont’d

46. 48
Evaluation of
the Methods

47. Flow diagram
Evaluation of the Methods
49
804 Patients assessed for study eligibility
66 Excluded
44 Did not meet entry criteria
738
Randomized
370 Randomized to
receive lefamulin
368 Randomized to
receive moxifloxacin
340 Completed treatment
28 Discontinued treatment
354 Completed trial
14 Discontinued trial
8 Adverse event
9 Lack of efficacy
3 Patient withdrew
2 Physician decision
1 Lost to follow-up
4 Sponsor decisiond
1 Missed last dose
9 Patient withdrew
3 Death
1 Lost to follow-up
1 Physician decision
345 Completed treatment
23 Discontinued treatment
11 Adverse event
8 Lack of efficacy
4 Patient withdrew
353 Completed trial
17 Discontinued trial
10 Patient withdrew
3 Death
1 Lost to follow-up
2 Did not receive lefamulin
1 Hospitalized
Cont’d

48. Flow diagram
Evaluation of the Methods
50
370 Randomized to
receive lefamulin
368 Randomized to
receive moxifloxacin
186 Included in the microbiological ITT
analysis
368 Included in the safety analysis
326 Included in the clinically evaluable test
of cure analysis
15 Did not meet CAP disease criteria
11 Test of cure visit outside window
9 Treatment <48 h (unless due to death)
8 Investigator assessment of clinical response
indeterminate at test of cure
0 Received potentially effective concomitant
antibiotics up to test of cure
2 Prior antibiotic deviation
5 Other confounding factor postbaseline up
to test of cure
205 Included in the microbiological ITT
analysis
368 Included in the safety analysis
330 Included in the clinically evaluable test of
cure analysis
2 Excluded (did not receive lefamulin)
12 Did not meet CAP disease criteria
14 Test of cure visit outside window
11 Treatment <48 h (unless due to death)
4 Investigator assessment of clinical response
indeterminate at test of cure
2 Received potentially effective concomitant
antibiotics up to test of cure
1 Prior antibiotic deviation
1 Other confounding factor postbaseline up
to test of cure
Cont’d

49. Evaluation of the Methods
51
• Phase 3
• Double-blind
• Double-dummy
• Parallel-group
• Randomized clinical trial
• 99 sites in 19 countries throughout Europe,
North America, South America, Asia, and
Africa
Study design
Intervention
Early clinical response (72
hours post 1st dose)
Test of cure (5-10 days
post last dose of study
drug)
Cont’d

50. Eligibility criteria followed
1:1 using a computer-generated central
randomization schedule with a block size of 6
Randomization was stratified by
• PORT risk class (II vs III or IV)
• Geographic region (US vs outside the US)
• Prior receipt of a single dose of short-acting
antibiotic therapy for CABP
Evaluation of the Methods
52
Cont’d
Patients:

51. Evaluation of the Methods
53
Ethical Considerations :
Approved by the ethics
committee or institutional
review board at each
participating site
In compliance with the
ethical principles of the
Declaration of Helsinki18
and the Good Clinical
Practice guidelines of the
International Conference on
Harmonization
An informed consent form
was signed by the patient
before initiating any study-
related procedures
Cont’d

52. Inclusion Criteria :
Evaluation of the Methods
54
Inclusion Criteria
3 or more CABP symptoms
(dyspnea, new or increased
cough, purulent sputum
production, and chest pain)
Acute illness
(≤7 days)
Adults with PORT risk class II,
III, or IV radiographically
documented pneumonia
Cont’d

53. Exclusion Criteria :
Evaluation of the Methods
55
Receipt of more than 1 dose of a
short-acting po/iv antibacterial
for CABP within 72 hours
before randomization
Hospitalization for 2 days or
longer within 90 days
Confirmed or suspected MRSA
Being at risk for major cardiac
events or dysfunction (eg,
known prolonged Q-T interval,
clinically significant
hypokalemia, clinically unstable
cardiac disease)
Significant hepatic disease
Cont’d

54. Intervention
Evaluation of the Methods
56
Intervention Dose Duration Route
Lefamulin
600 mg
bid
5 days
Minimum treatment duration
recommended for CABP
Treatment
po
Moxifloxacin
400mg
qd
7 days
Minimum approved
treatment duration according
to the moxifloxacin leaflet
po
Cont’d

55. Assessment of end points
 The US FDA primary efficacy end point
 Early clinical response at 96 hours (within a 24-hour
window) after receipt of first dose of either study drug in
the ITT population
 Patients were programmatically classified as responders if
they were
 Alive
 Showed improvement in 2 or more of the 4 CABP symptoms
 Had no worsening of any CABP symptoms
 Did not receive a nonstudy antibacterial for the current CABP
episode
Evaluation of the Methods
57
Cont’d

56. Assessment of end points
 The European Medicines Agency coprimary end points
 Clinical response at test of cure (5-10 days after last dose
of study drug) in the modified ITT population and in the
clinically evaluable population
 Investigator assessment classified patient responses
 Success if CABP was improved or resolved without
additional antibacterial
 Failure if the patient died from any cause or a nonstudy
antibacterial was required
Evaluation of the Methods
58
Cont’d

57. Lefamulin noninferiority vs moxifloxacin was concluded if the
lower limit of the 1-sided 97.5% CI for the treatment difference
exceeded –10%
• Continuity-corrected z statistic for early clinical response
• Miettinen and Nurminen method with adjustment for the randomization stratification
factors for investigator assessment of clinical response
The noninferiority margin of 10% was based on analysis of
observational studies comparing no treatment vs antibacterial therapy
• A 10%noninferiority margin preserves 50% of the treatment effect and is consistent
with FDA guidelines
Evaluation of the Methods
59
Statistical Analysis :
Cont’d

58. Statistical Analysis :
 Because this study was conducted at multiple study sites
 Post hoc analyses of early clinical response and investigator
assessment of clinical response were conducted using
hierarchical modeling to evaluate the potential for site effects
 Statistical analyses were conducted using version 9.2 or
higher of SAS software (SAS Institute Inc) which
includes
 Exact techniques for small data sets
 High performance statistical modeling tools for large data
tasks
 Modern methods for analyzing data with missing values
Evaluation of the Methods
60
Cont’d

59. Using a 79% responder rate in both treatment groups
for the ITT population
10% noninferiority margin
1-sided α level of .025
=> power=90% for early clinical response
Assuming a clinical response success rate :
For the modified ITT population 80%
For the clinically evaluable population at test of cure 85%
For clinical evaluability rate of 80%
This study had 91% power to demonstrate
noninferiority of lefamulin to moxifloxacin for
investigator assessment of clinical response at test of
cure
Using a 10% noninferiority margin
1-sided α level of .025
Evaluation of the Methods
61
Cont’d
Power Analysis:

60. 62
Evaluation of
the Results

61. 63
Evaluation of the Results
Baseline Characteristics
Cont’d

62. 64
Evaluation of the Results
Baseline Characteristics
Cont’d

63. 65
Evaluation of the Results
Baseline Characteristics
 The demographics and baseline characteristics were well
balanced between treatment groups
 Broadly representative of the patient population with CABP
 Percentages according to the per-protocol analysis
Cont’d

64. Primary Outcome:
66
Evaluation of the Results
Cont’d

65. 67
Evaluation of the Results
Cont’d
Secondary Outcome:

66. 68
Evaluation of the Results
Cont’d

67. 69
Evaluation of the Results Cont’d
Adverse Effects:

68. Adverse Effects:
 No cases of diarrhea led to study drug discontinuation
 Vomiting led to study drug discontinuation in 2
patients randomized to lefamulin and in 1 patient
randomized to moxifloxacin
 1 case of c. diff treated with oral vancomycin
 Both treatment groups reported low treatment-
emergent adverse event rates for hepatobiliary &
cardiac events
 Withdrawals and dropouts are discussed
70
Evaluation of the Results
Cont’d

69. 71
Evaluation of
the Discussion

70. Summary of Important Results
Evaluation of the Discussion
72
Cont’d

71. Suggested Mechanism :
 The suggested mechanism of action is
lacking
Evaluation of the Discussion
73
Cont’d

72. Evidence from other Studies
Evaluation of the Discussion
74
Cont’d

73. Clinical Implications:
Evaluation of the Discussion
75
Cont’d

74. Study Strengths
 Randomized design
 Evaluation of oral only short-course therapy
 A higher proportion of patients with more severe
forms of CABP
 Limited use of prior antibiotics
 Low drug and study discontinuation rates
 The use of moxifloxacin, a highly effective
antibiotic for treatment of CABP
 The use of multiple diagnostic modalities increased
the yield of baseline pathogen identification
Evaluation of the Discussion
76
Cont’d

75. Study Limitations :
 The extensive list of exclusion criteria may have limited the
generalizability of these results
 Many baseline pathogens were identified using nonculture
methods, limiting the collection of minimum inhibitory
concentration data
 Samples were not tested for viral co-pathogens
 Patients with suspected MRSA were excluded per protocol
due to poor coverage with moxifloxacin
 The overall recovery of resistant pathogens was low
 Race/ ethnicity designation may have been misclassified,
given that the methods (eg, self-reported vs solicited by
investigator in an open-ended or closed-ended fashion) to
collect these data may not have been consistent across sites
Evaluation of the Discussion
77
Cont’d

76. 78
Evaluation of
the Conclusion

77. Evaluation of the Conclusion
79
 Brief and clear
 Summarize the main points
Cont’d

78. 80
Overall
Evaluation

79. Lacks
Hypo-
thesis
Conflict
of
interest
Lacks
Suggested
mechanism
of action
MRSA
coverage
comparis
-on
group
Study Weakness
81

80. Study Strengths
82
Mentioned
limitations
Double
blinded
P-values
stated for
each
variable
Unbiased
conclusi-
on
Multi-
centered
Power
analysis
done

81. 83
Related Clinical
Trial

82. Related Clinical Trial
84
Title
• Omadacycline for Community-Acquired Bacterial
Pneumonia
Methods
• PSI risk class (II, III, or IV) receive
• Omadacycline (100 mg intravenously every 12 hours for
two doses, then 100 mg intravenously every 24 hours)
• Moxifloxacin (400 mg intravenously every 24 hours)
• A transition to oral omadacycline (300 mg every 24 hours)
or moxifloxacin (400 mg every 24 hours) respectively, was
allowed after 3 days; the total treatment duration was 7 to
14 days
Cont’d

83. Related Clinical Trial
85
Primary end point
• Improvement in at least two of four symptoms
(cough, sputum production, pleuritic chest pain, and
dyspnea) and no worsening of symptoms at 72 to
120 hours, without receipt of rescue antibacterial
therapy
Secondary end point
• Clinical response at a post-treatment evaluation 5 to
10 days after the last dose, with clinical response
defined as resolution or improvement in signs or
symptoms
Cont’d

84. Results • Omadacycline was noninferior to moxifloxacin for early
clinical response (81.1% and 82.7%, respectively
difference, 95% confidence interval [CI], −7.1 to 3.8)
• Rates of investigator-assessed clinical response at the
post-treatment evaluation were 87.6% and 85.1%,
respectively (difference, 2.5 percentage points; 95% CI,
−2.4 to 7.4)
• Adverse events that emerged after treatment initiation
were reported in 41.1% of the patients in the
omadacycline group and 48.5% of the patients in the
moxifloxacin group; the most frequent events were
gastrointestinal (10.2% and 18.0%, respectively)
Conclusion Omadacycline was noninferior to moxifloxacin for the
treatment of community-acquired bacterial pneumonia in
adults
Related Clinical Trial
86
Cont’d

85. 87
Reference
Evaluation

86. Evaluation of the References
88
The article included 27 references
• Correctly cited
• Up-to-date (majority in 2019) oldest in 2005
• Related to the topic
All the articles mentioned in the study were:
The authors didn’t cite themselves
• Primary : Journal
• Secondary : Book
They included the following literature :
Cont’d

87. References
89
1. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of
America/American Thoracic Society consensus guidelines on the management of
community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27
2. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med 2014;
371:1619
3. Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired
pneumonia in adults in Europe: a literature review. Thorax 2013; 68:1057.
4. File TM Jr, Goldberg L, Das A, et al. Efficacy and Safety of IV-to-Oral Lefamulin, a
Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial
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