serotype included within the 7-valent pneumococcal conjugate - ALAT

congresosalat.org

serotype included within the 7-valent pneumococcal conjugate - ALAT

Community Acquired Pneumonia:

Risk factors and antibiotic selection

Antonio Anzueto,

University of Texas Health Science

Center

San Antonio, USA


Disclaimer

Professional Relationships:

Member of the ATS/ERS Task force on COPD and COPD Exacerbations

Member of the ATS/IDSA 2001, 2003 and 2007 CAP guidelines Committee

Member of the Executive and Scientific Committee of GOLD

Advisory board, Consultant, Speaker:

Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Merck, Chiesi,

Bayer-Healthcare Pharma, Dey Pharma, Forest laboratories.

Grants:

NHLBI – COPD gene, LOOT

GSK – Eclipse, Horizon, Summit

Lilly - Severe Sepsis Trial

Stocks:

None


Clinical Case

– 62 -year-old retired teacher presented to

ED brought by daughter complaining 5

days of cough and flu like symptoms.

– He has history of prior “heart attack” and

maybe diabetes.

– Physical Examination:

• fever 101.7°F, HR 87/bpm,

RR 32/min, BP 70/40

• Left lower lobe crackles


CHEST X RAY


Antibiotic treatment…..

•What the likely pathogens ?

•How should I treat ?


Antibiotic treatment…..

•What the likely pathogens ?

•How should I treat ?


Etiology of Community-Acquired

Ambulatory

patients

S. pneumoniae

M. pneumoniae

H. influenzae

C. pneumoniae

Viruses

ICU = Intensive care unit

Pneumonia

Hospitalized

(non-ICU)

S. pneumoniae

M. pneumoniae

C. pneumoniae

H. influenzae

Legionella spp.

Aspiration

Severe

(ICU)

S. pneumoniae

H. influenzae

Legionella spp.

Gram-negative bacilli

Staphylococcus

aureus

Viral: H1N1

ATS/IDSA guidelines 2007.


PCVs have led to a shift in CAP aetiology

Hicks et al. JID, 2007; 196: 1346–54

Children


S. Pneumo serotypes

Lorking et al IDSA poster -2009


Serotype distribution: PCV-7 VT: serotype included within the 7-valent

pneumococcal conjugate vaccine; PCV-13 VT: serotype included within

the 13-valent pneumococcal conjugate vaccine;

NVT: non vaccine-type.

Bewick et al Thorax 2012


Risk Factors for PRSP & DRSP in CAP

• Age < 2 or 65 years

• β-lactam therapy, macrolides within 3

months

• Alcoholism

• Immune suppression (including steroids)

• Multiple medical comorbidities

• Exposure to child in daycare

IDSA/ATS 2007 Guidelines, CID 2007


Score System to Evaluate Risk MDRs

Aliberti et al, CID 2012:54


Antibiotic treatment…..

•What the likely pathogens ?

•How should I treat ?


Guidelines Concordance and Mortality

Mortensen, Restrepo, Anzueto, AJM 117: 726,2004


ATS/IDSA Algorithm for CAP

No

cardiopulmonary

disease

CAP is present

Outpatient therapy Inpatient therapy

History of

cardiopulmonary

disease

No modifiers +/- modifiers

+ C/P

Disease

+/or

Modifier

Mild to moderate

illness

No C/P

Disease,

No

Modifier

Severe CAP

Risks

Pseudomonas

Yes

No


Community-acquired Pneumonia:

Empiric Therapy – ATS/ IDSA

• INPATIENT

• General Ward: Resp Fluoroquinolone;

• -Lactam* + Macrolide

IDSA/ATS 2007 guidelines, CID 2007


Percent (%)

100

90

80

70

60

50

40

30

20

10

0

Moxifloxacin vs β-lactam/β-lactamase

Inhibitor ± Macrolide Combination

Therapy - Outcome

Moxifloxacin Comparator

*

**

93.4 85.4

93.7

81.7

n = 258 280 64 71

Clinical success Bacteriological

success


•Monotherapy with moxifloxacin is

superior (p


% Patients

60

50

40

30

20

10

0

Moxifloxacin vs β-lactam/β-lactamase

Inhibitor ± Macrolide Combination:

Time to Afebrile and IV-PO Conversion

Moxifloxacin Comparator

58.6 *

46.7

Patients Afebrile

Day 2

*P=0.025

50.2

17.8

n = 239 255 301 320


• Fast IV to oral conversion

• Faster fever resolution

IV to PO Conversion

Day 3

P=Not Reported † Amoxicillin-clavulanate +/- clarithromycin IV/PO.

IV formulation of comparators is not approved in the US.

Finch R et al. Antimicrob Agents Chemother. 2002;46:1746-54.


*** p


Success rate (% of patients)

100

CAPRIE: clinical outcomes

80

60

40

20

0

Clinical recovery rate

(95% CI: 1.7, 14.1); P=0.01

97.9

Anzueto et al. Clin Infect Dis 2006; 42: 73–81

Moxifloxacin Levofloxacin

Clinical cure rate

(95% CI: –1.9, 11.9); P=0.2

92.9

90.0 87.9

138/141 126/140 131/141 123/140

Days 3-5 Test of cure


MOXIRAPID Clinical Trial:

Faster Fever Resolution in CAP

Moxifloxacin

(n=161)

Day 3.8

Ceftriaxone ± macrolide

Day 4.8

P =0.0027

0 1 2 3 4 5 6

Mean time to defervescence (Days)

Welte T, et al. Clin Infect Dis 2005; 41: 1697-1705

Fever Resolution

(n=156)


MOXIRAPID Clinical Trial:

Faster IV/PO Switch and Hospital Discharges

IV/PO Switch Hospital Discharges

Moxifloxacin (n=161)

Day 5.4

Ceftriaxone ± macrolide

(n=156)

Day 9.5

0 2 4 6 8 10

Number of days on IV therapy

Welte T, et al. Clin Infect Dis 2005; 41: 1697-1705

Moxifloxacin (n=161)

Day 9.8

Ceftriaxone ± macrolide (n=156)

Day 11.1

p = 0.0005

0 2 4 6 8 10 12

Mean number hospitalization days


CAP: Overall Treatment Cost

# p=0.018 (p-value compared to CURB-65 score 0)

¶ p


Pharmacodynamic Profile

Efficient Penetration of Moxifloxacin*

Bronchial

Mucosa

n=8

Alveolar

Macrophages

n=5

5.5

0 1 2 3 4 5 6 7 8 60 65

Mean Concentration ( g/g or mg/L)

61.8

Achieves tissue levels at 3 hours well above MIC 90s † for key RTI pathogens

Capitano B et al. Chest. 2004 Mar;125(3):965-73.


Pharmacodynamic Profile

Moxifloxacin versus Levofloxacin

Lung Tissue Penetration after 24 Hours*

Alveolar

Macrophages

**p=0.04

Epithelial

Lining Fluid

†p=NS

2.9

5.7


Levofloxacin Moxifloxacin

n=15 n=16

8.2

32.8 **

0 10 20 30 40

Tissue Concentrations (mg/L)

Capitano B et al. Chest. 2004 Mar;125(3):965-73.


Moxifloxacin serum concentrations in

critically ill patients

Pletz et al ICM 2010; 36:979


Moxifloxacin plasma and bronchial

concentrations in MV patients

Leone et al Antimicrobial Agent and Chemo 2004; 48; 638


Ongoing challenges in the

Management of CAP

• CAP continue to be an important cause of

morbidity and mortality

• S. pneumoniae is the most frequent pathogen

isolated in CAP, with increased bacterial

resistance.

• Fluoroquinolones, especially moxifloxacin, is a

viable therapy option in CAP patients.

• Outcomes may be improved and antimicrobial

resistance slowed if guidelines are applied


-Klebs in 1875 was

the first person

described

presence of

bacteria in the

airway of a patient

who died

of pneumonia.

More magazines by this user
Similar magazines