RTI (adults) 10:30-10:45 Respiratory tract infections in the adult - - PowerPoint PPT Presentation

Nov 16, 2001 Workshop #6 : RTI in adults

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• C. Carbon, Paris

RTI (adults)

10:30-10:45 Respiratory tract infections in the adult (ambulatory and hospital-treated)

Nov 16, 2001 Workshop #6 : RTI in adults

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Macrolides in RTIs: Adult patients Claude Carbon Division des Maladies Infectieuses CHUV; CH-Lausanne

Nov 16, 2001 Workshop #6 : RTI in adults

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Introduction

• Major source of AB use: 67% (Garau, 2001)
• 1/6 physician visits in US or Canada.

(Gonzales, 1997).

• France: frequency of Dg and AB-Rx RTIs

increased by 86% in adults in a 10-y period

(Guillemot, 1998)

• Vast majority of viral origin.
• High % of undue courses of AB

Nov 16, 2001 Workshop #6 : RTI in adults

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Major pathogens

• URTIs: Streptococcus pneumoniae,

Haemophilus influenzae, group A strep.

• LRTIs: S.pneumoniae, H.influenzae, Moraxella

catarrhalis,intracellular pathogens

• All are within the spectrum of activity of M.
• Drawbacks: resistance (R), poor intrinsic

activity against H. inf., lack of cidal effect.

• Impacts of R: risk of failure (Garau, 2001);

reconsideration of M as first line choice.

Nov 16, 2001 Workshop #6 : RTI in adults

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Clinical use of M in RTIs

• Frequent drawbacks in clinical studies: Dg,

assessment of severity, lack of power…

• Sinusitis: 90% maxillary; > 50% self-

limited.(Williams, 1999)

• M no longer considered as first choice.
• Bronchitis: *acute: no AB Rx. *AECB:AB

restricted to the most severe cases. Efficacy

• f M compromised by R of S.pneumoniae

Nov 16, 2001 Workshop #6 : RTI in adults

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AECB

• Ery. mentioned as one of the first line choice
• nly in US recommendations, and as a

second line choice in European guidelines (Ball, 1998)

• Poor effect against H.influenzae (failure;

persistence) (Davies, 1989; Beghi, 1995)

• Main problem: to restrict AB use to pts with

the most severe presentations

Nov 16, 2001 Workshop #6 : RTI in adults

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Community-acquired pneumonia

• Common practices in Europe (Huchon, 1996):

– F/UK: β-lactams; E: M; D:Tc; I: 3-CSP

• Good evaluation of severity(Schaberg, 1996;

Fantin, 2001; Bochud, 2001)

• Contradictory evaluation of the impact of

guidelines:clinical/economical outcomes

• 4 classes of Pts: risk factors, severity and

prediction of mortality(ATS,1993)

Nov 16, 2001 Workshop #6 : RTI in adults

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CAP: Guidelines

• US/Canada:M = one of the first line choice for

group 1. Combined with other AB in the other groups.(Bartlett, 2000; Mandell, 2000)

• Europe (Woodhead, 1998):

– non severe CAP: F:amox or M; I:β L ± M; UK:amox; E: penicillin or M – severe CAP: F: coamox (or 3CSP) + M; I/E: 3CSP + M; UK: 2CSP + M

Nov 16, 2001 Workshop #6 : RTI in adults

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Comments

• In outpatients: M cannot be recommended as

monotherpy if any risk of S.pneumoniae. First group of ATS.

• In elderly: FQ, or 2CSP (3CSP) + M: reduced

mortality at d 30 vs other regimens (Gleason,

1999)

• Low cost AB not necessarily associated with

poor outcomes (Gilbert, 1998)

Nov 16, 2001 Workshop #6 : RTI in adults

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Which macrolide (I) ?

• Ery. = reference. Poor validation of some

concepts (targeted AB, synergy C/OH-C) (Carbon

2001)

• With some compounds (M16, dirithromycin)

limited evaluation of efficacy(severe cases, bacteremia). No studies vs FQ against

• Legionella. M less cidal (Edelstein, 1998)
• Azi. not convenient for bacteremic patients

(Fogarty,1998 ) failure of Roxi. to cure H. influenzae (Ortqvist, 1996)

Nov 16, 2001 Workshop #6 : RTI in adults

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Which macrolide (II) ?

• Basis for choice:

– Rx habits; tolerance; drug interactions; extracellular concentrations; R patterns: 16 M vs 14-15 M? Little is known about the consequences

• f R profile vs efficacy of 16 M and of their
• veruse on R. (Klugman, 1998)
• Risks of underdosing (limited adaptability)

and risks of increased selection of R with long acting compounds (Baquero,1999)

Nov 16, 2001 Workshop #6 : RTI in adults

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Ketolides

• Telithromycin. 800mg OD.
• Six phase III studies in CAP: 3 comparative

(Amox, trova, clari), 3 non comparative.

• 1400 pts treated with T. 90% clinical cure;

90.5% bacteriological cure.(Carbon, 2001)

• No impact of age, severity, bacteremia.
• Limits: small numbers of Ery R S.pn.
• Effect vs H.infl.? Impact of R mechanisms ?

Nov 16, 2001 Workshop #6 : RTI in adults

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Conclusions

• M cannot be longer considered as first line

monotherapy for Rx of RTIs in adults.16 M to be better investigated. Significant threshold of R ?

• Ketolides represent a potential alternative.
• Newest FQ competitors for single drug Rx in

CAP

• Need for improving Dg, restricting AB

indications.