Beruflich Dokumente
Kultur Dokumente
Dr Andrew Fuller
Basic Principles
1. Are antibiotics needed?
2. Narrow spectrum
3. Appropriate choice
4. Least number
5. Allergies
6. Cultures prior
7. Combination therapy needed
8. Oral vs IV
9. Prophylaxis
10. Avoid topical
Mechanisms of antibiotic action
Classification of Antibiotics by Target Site of Activity
Target site Drugs Usual activity
3. 1.
2.
4.
1. Antibiotic inactivation
E Enterobacter species
S Serratia species
C Citrobacter species
A Acinetobacter species
P Pseudomonas aeruginosa
P Proteus vulgaris (ie. indole-positive Proteus species; not P. mirabilis)
M Morganella morganii
1. Antibiotic inactivation
(c) Aminoglycoside modifying enzymes:
2.
4.
2. Alteration of target sites
These are associated with enzymatic functions essential for cell wall
synthesis and remodelling, and vary in number and size depending on the
bacterial species.
2.
4.
3. Decreased antibiotic permeability
2.
4.
4. Active Efflux
1. Beta-lactams
1.1 Penicillins
Anti-staphylococcal penicillins
Moderate-spectrum penicillins
Broad-spectrum (anti-Pseudomonas aeruginosa) penicillins
1.2 Penicillin + b -lactamase inhibitor combinations
1.3 Cephalosporins
1.4 Carbapenems
1.5 Monobactams
Antibiotic Classes
2. Glycopeptides
3. Aminoglycosides
4. Macrolides
5. Tetracyclines
6. Antifolate agents
7. Fluoroquinolones
8. Rifamycins
9. Nitroimidazoles
10. Others- Chloramphenicol, clindamycin, fusidic acid,
nitrofurantoin and spectinomycin. Linezolid. Daptomycin.
Ceftaroline.
1. Beta-lactams
b -Lactams are structurally related, in that they all have a b -lactam
ring; all primarily act by binding with PBPs to inhibit cell wall synthesis
and/or repair and in most cases all classes are bactericidal.
Among patients with acute Epstein Barr virus infection (glandular fever),
both drugs are similarly associated with the production of a prominent
erythematous rash - however this does not indicate true allergy.
1.1 Penicillins
Broad-spectrum penicillins
Piperacillin and ticarcillin are active against Pseudomonas aeruginosa, but are
generally administered in combination with a second anti-pseudomonal drug
such an aminoglycoside.
Both drugs are available only in parenteral form. Both agents have been
combined with a b-lactamase inhibitor (see below) to broaden their spectrum:
piperacillin/tazobactam and ticarcillin/clavulanate.
Ceftazidime.
Fourth-generation cephalosporins:
cefepime and cefpirome
1.3 Cephalosporins
1.3 Cephalosporins
Fifth-generation cephalosporins:
Ceftaroline
Ceftaroline is a cephalosporin with activity against Gram positive and
Gram negative bacteria. C
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Meropenem has the advantage of fewer side-effects and 8-hourly dosing (cf 6
hourly dosing for imipenem), but is cheaper. Both agents may be associated
with antibiotic-associated diarrhoea, presumably due to their impact on the
natural bowel flora. Meropenem attains better CSF levels than imipenem and
is preferred if CSF penetration is important.
1.4 Carbapenems
Doripenem
Ertapenem
Aztreonam is the only drug in this class. It is notable since it has good
activity against Gram- negative pathogens, but is inactive against Gram-
positive organisms and anaerobes.
• Gentamicin
• Tobramycin
• Netilmicin
• Amikacin.
• Streptomycin
• Framycetin
• Neomycin
4. Macrolides
Macrolides include erythromycin, roxithromycin, azithromycin and
clarithromycin.
They have a wide spectrum of activity including Gram-positive cocci such
as streptococci and staphylococci, as well as so-called "atypical" pathogens
such as Legionella, Mycoplasma and Chlamydia spp.
They are also active against Bordetella pertussis (whooping cough),
Corynebacteria and some strains of H. influenzae. Notably, they have no
activity against enteric Gram-negative bacilli and resistance among S.
pneumoniae and S. aureus is increasing.
Erythromycin has a number of oral formulations which have variable
absorption and are frequently associated with gastrointestinal side effects,
particularly nausea. Rarely, hepatotoxicity may occur. Parenteral
erythromycin is frequently associated with painful phlebitis at the injection
site and therefore needs to be given slowly or even through a central
venous catheter.
4. Macrolides
Roxithromycin is an alternative to oral erythromycin as it has good oral
availability, but less gastrointestinal side effects.
The newer macrolides, clarithromycin and azithromycin, are more reliably
absorbed and have longer half-lives than erythromycin, allowing less
frequent dosing. They attain high intracellular concentrations and therefore
may be more effective for intracellular pathogens.
Azithromycin has good in vitro activity against a wide range of organisms
including H. influenzae. It is notable for its once-daily dosing which is
particularly useful for the treatment of chlamydial sexually transmitted
diseases, as well as trachoma and donovanosis.
Clarithromycin has similar activity to azithromycin, but in addition, is
active against Mycobacterium avium complex in patients with HIV
infection. For this indication it has proven effective for both prophylaxis
and treatment.
5. Tetracyclines
Tigecycline
50mg bd IV
is a tetracycline class antibiotic in the glycylcycline subcategory for
intravenous infusion.
Used for MRSA, VRE, resistant mycobacteria eg m.abscessus
Activity against atypicals, anaerobes.
Not pseudomonas and some other gram negatives
Blood levels poor – not for septicaemia
Nausea
6. Antifolate agents
Trimethoprim and sulfamethoxazole both have anti-folate activity that impairs
satisfactory DNA production. Except in combination with trimethoprim as
cotrimoxazole, sulphonamides have little place in clinical practice (apart from their
use in the treatment of cerebral toxoplasmosis). For many of the indications
previously considered to require cotrimoxazole, trimethoprim alone has now been
found to be as effective, especially for the treatment of urinary tract infections.
They generally need to be used in combination with other agents to avoid the rapid
emergence of resistance.
Both agents are potent inducers of hepatic P450 activity and therefore interactions
with other drugs need to be noted.
Rifampicin is one of the few orally available agents active against MRSA - in this
situation it should be used in combination with either fusidic acid or ciprofloxacin.
Metronidazole and tinidazole are nitroimidazoles - both are notable for their extremely
broad activity against Gram-positive and Gram-negative anaerobes (e.g. Clostridia
species, Bacteroides fragilis) and anaerobic protozoa including Trichomonas
vaginalis, Giardia lamblia and Entamoeba histolytica.
Metronidazole is the drug of choice for the treatment of Clostridium difficile
diarrhoea. Metronidazole is available in both oral and intravenous preparations as well
as suppositories.
Metronidazole is commonly combined with ampicillin and gentamicin for the
treatment of serious intra-abdominal sepsis, or wherever substantive anaerobic activity
is required.
Tinidazole is only available as an oral preparation and but its long half-life allows
once-daily dosing. Both drugs may cause a disulfiram (antabuse-like) reaction if
alcohol is consumed concurrently.
10. Others
Clindamycin is a lincosamide with activity against Gram-positive aerobes and
most anaerobes. It also has activity against Toxoplasma gondii. It is useful since it
is available in both intravenous and oral preparations, but is expensive and may be
associated with antibiotic-associated diarrhoea.
It is available in injection and tablet form. Doses are equivalent as the drug is highly
bio-available. Eg 600mg orally BD.
For MRSA infections, its cure rate compared to vancomycin is equivalent. At present it
is not indicated for use more than 28 days. Its current price @ $125.00 per tablet makes
it the most expensive oral antibiotic.
10. Others
SYNERCID (Dalfopristin, Quinupristin)
This drug is now not available for treating methicillin-resistant Staph aureus,
vancomycin- resistant Enterococcus faecium. It is not active against Enterococcus
faecalis. It is only available in intravenous formulation, which is extremely expensive.
Dose: 7.5 mgs per kilogram 8-hourly. Synercid i.v. is given through a peripherally
inserted central catheter because of its ability to cause severe venous irritation.
Major side effects include: Local effects; raised LFTs; arthralgia, myalgia;
superinfection; rash; GI upset
Drug interactions: Drugs metabolised by CYP3A4 eg cyclosporin A, midazolam,
nifedipine, esp. drugs which prolong QT interval eg terfenadine, astemizole, cisapride,
disopyramide, quinidine, lignocaine (avoid concurrent use)
The two components (called streptogramins) are bacteriostatic drugs that act on
the bacterial ribosome; however, when combined, these drugs work in a bactericidal
fashion by inhibiting early and late phases of bacterial protein synthesis. It is extremely
expensive.
Endocarditis
Meningitis
Empiric therapy benzylpenicillin ceftriaxone
+ ceftriaxone/cefotaxime or chloramphenicol
Brain abscess
Empiric therapy benzylpenicillin
+ metronidazole
+ ceftriaxone/cefotaxime
Post-operative vancomycin
+ ceftriaxone/cefotaxime
Toxoplasmosis sulfadiazine clindamycin
+ pyrimethamine (+ folinic acid) + pyrimethamine
Commonly recommended antibiotic regimens for various conditions
Gastrointestinal infectious
Enteric fever (typhoid, paratyphoid) ciprofloxacin ceftriaxone/cefotaxime
cotrimoxazole 4
amoxycillin 4
chloramphenicol 4
Pancreatitis
Acute: None
Necrotising: ticarcillin/clavulanate ceftriaxone/cefotaxime
+ metronidazole
Pyogenic liver abscess Similar to acute peritonitis due to perforated viscus 10
Commonly recommended antibiotic regimens for various conditions
Acute cystitis
Non-pregnant females: trimethoprim cephalexin
amoxycillin/clavulanate nitrofurantoin
Acute pyelonephritis
Mild-moderate cephalexin amoxycillin/clavulanate
trimethoprim
norfloxacin
Prostatitis
Acute-severe: amoxy(ampi)cillin IV
+ gentamicin
Lower RTI..
Exacerbations of chronic bronchitis amoxycillin doxycycline
Community-acquired pneumonia:
Mild: roxithromycin amoxycillin
doxycycline
Moderate penicillin IV 14
+ roxithromycin
Severe 15 erythromycin IV
+ ceftriaxone/cefotaxime
or penicillin IV 16
Septicaemia
clindamycin
+ gentamicin
Commonly recommended antibiotic regimens for various conditions
Septicaemia
+ gentamicin
Pneumonia Children: di(flu)cloxacillin
+ ceftriaxone/cefotaxime
Adults: erythromycin erythromycin
+ ceftriaxone/cefotaxime + penicillin
+ gentamicin
Other Infections
Q fever (Coxiella burnetii) doxycycline chloramphenicol