The therapy of respiratory infections

1. The therapy of respiratory infections Dr Heidi Orth Dept Medical Microbiology

2. Upper respiratory infections (URTI)

3. Pharyngitis/TonsillitisCauses • Resp viruses – most common • Bacteria – 5-30% • Group A -hemolytic streptococci (GABHS) (S. pyogenes) • Non-infective causes – allergy; exposure to irritants

4. Rx Streptococcal pharyngitis/tonsillitisto prevent complications • Penicillin • Pen V x 10 days • Benzatine penicillin (IMI injection) Alternatives: • Amoxycillin x 10 days • Better absorption • Skin rash may follow if EBV pharyngitis – may diagnose incorrectly as pen allergy • Only indicated if pos culture with GABHS

5. Short course therapy (3-5 days) • 5 days: e.g. Amoxicillin/clavulanate; Clarithromycin; oral cephalosporins • 3 days: • Azitromycin

6. Acute otitis media (AOM) • Viruses • Bacterial causes: • Streptococcus pneumoniae • Haemophilus influenzae (non-typeable) • Moraxella catarrhalis • Indications for antibiotics: • Recurrent AOM • Immunocompromised pt • <2yrs • Structural ENT abnormalities • Fever>38C or pain>48hrs • Daycare attendees

7. Selected cases - observation on symptomatic treatment only • Observe for 48-72hrs without antibacterial Rx in selected cases • >2yrs with non-severe AOM or where diagnosis uncertain • Requires good follow up and presence of adult that can monitor the child • Give Paracetamol or Ibuprofen for pain • Decongestants – use in AOM controversial, topically x 3 days rather than orally

8. Rx of AOM in children • High dose Amoxicillin 90mg/kg/day in 2-3 divided doses 5-7days – drug of choice • 7-10 days therapy for <2yrs; recurrent/chronic AOM and complicated cases • If fever>72hr on appropriate therapy, refer to ENT specialist for tympanocentesis and cultures

9. Alternatives • Amox/clav – also effective against B-lactamase producing H. influenzae and M catarrhalis – if no response on amox alone; first line for severe disease (T39C, severe otalgia) • Oral cephalosporins: cefuroxime and cefpodoxime - not effective against high level penicillin resistant pneumococci • Parenteral cephalosporins (Ceftriaxone) – for severe cases e.g. mastoiditis or where no response on high doses amox/clav; or if vomiting and not tolerating oralmeds • Macrolides e.g. azithromycin/clarithromycin– if allergic to penicillin

10. AOM with otorrhoea in patients with tympanostomy tubes (TT) • Culture of otorrhoea fluid in patients with TT often yield bacteria such as Pseudomonas and Staphylococcus aureus. • These pathogens can be treated with topical ciprofloxacin drops

11. Prevention of AOM • 7-valent pneumococcal vaccine • Recently introduced in S.A. (Prevenar) • Also now in public sector available • End 2008 launched in Eastern Cape • 2009 – other provinces

12. Acute bacterial sinusitis(ABS) • Predisposing factors: • Viral URTI • Allergy, trauma or tooth infection may lead to inflammation of nasal and para-nasal sinus membranes • Bacterial causes: • Streptococcus pneumoniae • Haemophilus influenzae • Moraxella catarrhalis Less common • Other streptococci; anaerobes and Staphylococcus aureus • Chlamydophila pneumoniae – chronic sinusitis • Fungi – immunocompromised patients

13. Important factors • Recent antibiotics - select for resistant organisms • Duration of Rx: 10 days • New agents: moxifloxacin (fluoroquinolone) 5-7 days • No clinical response (persistent fever) after 72hr with appropriate antibiotics - refer to ENT specialist – CT scan, endoscopy or sinus aspiration and cultures may be indicated • Penicillin allergy – if reaction to penicillin only itchy, maculopapular skin rash, use cephalosporin

14. Rx of ABS +AOM (Adults) Children: amoxycillin 90 mg/kg/d (3 divided doses) x 10 days Adults: amoxycillin 1g 8hrly x 10 days • alternatives: • Amox/clav; Oral cephalosporins; Macrolides; Fluoroquinolones e.g. moxifloxacin • No response to first line drugs: • Amox/clav with high dose amox • Ceftriaxone, IV of IM x 3-5 days if severe infection e.g. peri-orbital inflammation, intra-cranial or extra-sinus complications • Fluoroquinolones

15. Lower respiratory infection • Acute bronchitis/Acute on chronic bronchitis? • Community-acquired pneumonia • Hospital-acquired pneumonia

16. Community-acquired Pneumonia (CAP) • Causes: • Streptococcus pneumoniae • Atypical pathogens – Mycoplasma pneumoniae; Chlamydophila pneumoniae; Legionella – cyclic and geographical variation • Respiratory viruses – Influenza A& B • Haemophilus influenzae - COPD • Gram negative Enterobacteria e.g. Klebsiella – elderly; neonate; high morbidity/mortality • Staphylococcus aureus – high morbidity/mortality

17. Other causes • Polymicrobial – elderly; severe ill patient • Oral anaerobic flora – aspiration (alcoholic; epilepsy; Stroke) • Mycobacterium tuberculosis • HIV +ve pt: • Same as HIV -ve pt • Most common: S. pneumoniae; H. influenzae • Also S. aureus and Gram neg orgs and unusual causes e.g. Pseudomonas aeruginosa and opportunistic pathogens (Pneumocystis) • Pseudomonas • Structural lung disease (cystic fibrosis, bronchiectasis) • Broadspectrum antibiotics in previous month • Recent hospitalisation • Recent Antibiotics exposure in past 3 months: risk for resistance • Do not use same antibiotics; use different class, or in case of beta-lactams a broader spectrum agent

18. Antibiotic choice/Hospitalisation? • Age (<65yrs versus >65yrs) • Co-morbid disease: • HIV • Chronic heart/lung disease • Renal disease • Liver disease • Diabetes mellitus • Severity of infection – tagipnea, low BP, patient confused?

19. Empiric antibiotics

20. alternatives Rx

21. Addisional Rx • Macrolides (erythromycin; clarithromycin) or • Azalides (azithromycin) or • Tetracyclines (doxycycline) • Not recommended as monotherapy due to high incidence of resistance in S. pneumoniae • As addisional therapy if infection with ‘atypicals’ is suspected or no response on initial Rx

22. Duration of treatment • Empirical treatment – start as soon as possible, recommend within 4-8hrs of presentation (better outcome) • Optimal duration is uncertain Guidelines: • Elderly; co-morbid disease and HIV pte may require longer Rx • IVoral drugs when good clinical response within 48-72hrs • 5-7 days for typical causes • 14 days for atypicals: Mycoplasma; Chlamydia and Legionella • Give attention to: bed rest, analgesia, nutrition, hydration, oxygenation; support cardiovacular & renal function

23. Penicillins •  in resistance in S. pneumoniae, due to penicillin-binding protein (PBP) mutations – for resp infections high dose IV treatment will still be effective • H. influenzae – beta-lactamase production may occur conferring resistance to amoxicillin  amox/clav effective • Examples • Penicillin • Ampicillin • Amoxycillin • Amox/clav

24. Macrolides/Azalides • Increasing resistance in pneumococci • Not appropriate as monotherapy • Agents of choice for atypical pathogens • Examples • erythromycin • clarithromycin • azithromycin (azalide)

25. Cephalosporins • Oral cephalosporins:cefuroxime (2nd gen); cefpodoxime (3rd gen) • Good activity against staphylococci • IV and PO • 3rd gen. cephalosporins: ceftriaxone; cefotaxime: • Greater Gram negative cover • Due to emerging resistance to cephalosporins in pneumococci high dosages are recommended

26. Aminoglycosides • Only as part of combination therapy in severely ill patients for Gram negative cover of Enterobacteria e.g. Klebsiella, E.coli. • Can be discontinued if another pathogen is isolated. • Avoid aminoglycosides in the elderly • Gentamycin • Amikacin • Tobramycin

27. Fluoroquinolones • New agents have better pneumococcal cover • Effective against typical and atypical pathogens • Contra-indications – recent treatment with a fluoroquinolone - due to development of resistance • Moxifloxacin • Levofloxacin

28. Carbapenems - Ertapenem • Broad spectrum agent • Active against pneumococci; anaerobes; most Enterobacteria (including ESBLs ‘extended spectrum beta-lactamase producers’) • Not active against nonfermenting Gram negative organisms e.g. Pseudomonas, Acinetobacter • Indications: • Elderly with co-morbid illness and/or in longterm care facility or alcoholic • Aspiration pneumonia/suspected anaerobic infection/lung abscess • Cases known or suspected of being infected with resistant pathogens • Failed first line treatment, usually based on microbiological culture results

29. Tetracyclines • Doxycycline has good activity against H. influenzae, but increasing resistance in pneumococci • Alternative in areas with low resistance or additional therapy against atypical pathogens • Doxycycline

30. response on therapy • With appropriate therapy a clinical response should occur within 24-72hrs. • Elderly/Co-morbidityresponse slower • if response not optimal, take the following into account: • Is the therapy appropriate? • Is this an unusual pathogen e.g. Pneumocystis? • Does the patient have TB? • Non-infective disease e.g. pulmonary embolus/carcinoma? • Complications e.g. empyema, sepsis?

31. Hospital-acquired pneumoniaCauses • Post-aspiration e.g. stroke – oral anaerobic flora + S. pneumoniae • Mechanical ventilation – Gram negative Enterobacteria; Pseudomonas aeruginosa

32. Microbiology of nosocomial pneumonia (NP) • Early or late onset • Severity of infection (ICU or non-ICU) • Risk factors for multi-resistant Gram negative pathogens e.g. Pseudomonas, Acinetobacter, ESBL producing Klebsiella pneumoniae • Recent antibiotics (previous 3mths)/hospitalisation (for period of 5 days)

33. Microbiology of NP • Early onset NP within 4 days/non-ICU – S. pneumoniae; Haemophilus influenzae, MSSA, Moraxella & antibiotic-S Gram negative bacilli e.g. Klebsiella, E. coli etc. • Late-onset NP/ICU/Ventilation-associated pneumonia (VAP) –same pathogens, but often more resistant e.g. MRSA, multi-resistant Gram negative bacilli e.g. ESBL-producing Klebsiella, also Pseudomonas, Acinetobacter

34. Hospital acquired pneumoniano empirical regimen covers all causesDo cultures before starting antibiotics!

35. References • Management of community-acquired pneumonia in adults. SAMJ December 2007, Vol 97, No 12 • Guideline for the Management of Upper Respiratory Tract Infections. SAJEI 2008, Vol. 23, No. 4 Updated Jan 2012