Lecture - Antimicrobial Action In Resp Disease Flashcards
Pathogen for community aquired pneumonia
- Strep pneumonia : 15-76%
- H. Influenzae
- Legionella
- Mycoplasma pneumonia
- chlamydophila pneumonia
- viruses
- oral anaerobes
- staph aureus
- Gram neg
- unknown
Antibiotic guidelines: community-acquired pneumonia in adults: moderate disease
- benzylpenicillin 1.2g IV, 6 hourly until significant improvement
- then amoxyxillin 1g orally, 8 hourly for a total of 7 days
- plus doxyccline 100 mg orally, 12 hourly for 7 days
Community acquired pneumonia in adults: severe disease
- ceftriaxone 1g IV, daily
- plus azithromycin 500 mg IV, daily
Typical bacteria
- pathogens
- antibiotic
- strep pneumonia
- H influenza
- narrow specrtrum b lactams first
- if doesnt work: macrolides, tetracyclines, new quinolones
Bacteria: atypical
- Mycoplasma pneumonia
- chlamydia pneumonia
- C. Psittaci
- Legionella species
- b lactams ineffective
- macrolides, tetracyclines, or quinolones
Anaerobes
- treatment
- penicilin
- metronidazole
- clindamycin
Hospital acquired
- pathogens
- treatment
- pseudomonia aeruginosa and other gram neg rods
- MRSA
- treatment: broad spectrum b-lactams +/- aminoglycosides, quinolones, vancomycin, linezolid
Causes of chest infiltrates in AIDS patients
- pneumocystis jiroveci (PJP)
- mycobacteria TB, mycobacteria avium
- nocardia
- legionella
- typical bacterial pathogens
- cytomegalovirus
Fungi
- pathogens
- treatment
- Dimorphic fungi, Aspergillus, C. Neoformans
- Treatment: amphotericin B, triazoles, echinocandins
- Pneumocystis jiroveci
- Treatment: sulphonamides + DHFR inhibitors, pentamidine, atovaquone
Viruses
- influenza
- Treatment: neuraminidase inhibitor (Oseltamivir)
S pneumonia infection: presentation
- sudden onset
- productive cough
- Fever, chills, pleuritic pain
- Gram stain highly specific
M pneumonia
C pneumonia
Presentation
- Prodrome 4-5 days
- Non purulent cough
- URT symptom
- Extra thoracic symptome
Effective antibiotic use
- active against bacteria likely to be at the site of infection (eg: S pneumonia/lung)
- Good penetration and concentration at site of infection
- stay at high level for long enough to eradicate the bacteria (Time>MIC)
- narrowest spectrum for shortest duration
- stop if viral aetiology confirmed and bacterial infection unlikely
B-lactams antibiotics
- include penicillins, cephalosporins and carbapenems
- inhibit bacterial cell wall synthesis
- are bactericidal can be given in large doses
- are not concentrated in cells
- may be slowly or rapidly excreted
- are destroyed by bacterial b-lactamases
Bacterial resistance mechanisms
- entry or active efflux
- modified target
- inactivating enzymes - b-lactamase
- intinsic or acquired
- chromosomal or plasmid
Minimum inhibitory concentration
- the lowest concentration in a dilution series of set antibiotic that completely prevents growth of the organism
- antibiotic needs to be 40% of the time above the MIC
- breakpoint concentration
- think about where the pathogen has infected as well
S pneumonia b-lactam resistance
- incremental
- Rising MIC
- follows multiple mutations in PBP genes
- altered binding affinity for penicillins and cephalosporins
H influenzae b-lactam resistance
- Frequencu of the TEM-1 b-lactamase: hydrolyses penicillin, ampicillin and amoxycillin
Mycoplasma and chlamydophlia
- mycoplasmas do not have cell walls and are therefore not destroyed by b-lactams
- chlamydia are obligate intracellular bacteria, incapable of synthesizing aTP
- they multiply in the phagosomes of phagocytic cells
- this is an all or nothing resistance
Fluoroquinolones
- Norfloxacin: renal tract infections
- Ciprofloxacin: gram - sepsis, including pseudomonas aeruginosa and legionella
- Moxifloxacin: respiratory quinolones: spectrum includes pneumococci
Aminoglycosides
- Gentamicin, tobramycin, Amikacin
- excreted only by glomerular filtration and accumulate if renal function is poor
- no activity against stric anaerobes
- most useful for aerobic Gram neg
- inherently nephro and neurotoxic
- synergistic in combination with b-lactams
Systemic antifungal agents
- ergosterol plasma membrane integrity
- polyenes: amphotericin B
- ERgosterol biosynthesis inhibitors: Azoles
- GLucan synthesis inhibitors: Echinocandins
Drug development and antibiotic resistance
- drug evaluation defines the spectrum of activity
- laboratory tests estimate the likelihood of resistance develop
- emergence of resistance will only become apparent with clinical use
- the degree and rate will depend on level of use
Bacterial antibiotic resistance
- the driving force of antibiptic resistance is widespread antibiotic use
- 40-50% of acute care inpatients receive antibiotics as treatment or prophylaxis
- many studies show excessive and inappropriate medical prescribing