general considerations (1) Flashcards
CHARACTERISTICS of ANTIBIOTIC THERAPY
causative therapy
the pathogens actively response to the challenge
antibiotic use is a permanent interference with the
environment
TYPES of ANTIBIOTIC THERAPY
empiric
sensitivity based (definitive, pinpointed)
prophylactic
Infications for prophylactic treatment
surgical prophylaxis - cephalosporins
non- surgical prophylaxis
individuals with high risk
e.g. immunocompromised patients, patients with endocarditis
recurrent infections
e.g. urinary, genital herpes, otitis media
close contacts e.g. meningococcal infection, tuberculosis, pertussis, plague etc.
risk of infection (endemic regions) e.g. malaria, anthrax
The basic condition of an effective therapy
- the pathogens have to be sensitive to the antimicrobial agent
- the antimicrobial agents have to be in effective cc. at the site of infection, which depends
- on the pharmacokinetics of the drug
- on the route of administration
- on the dose
- on the duration of the therapy
- T>MIC - time-dependent antibacterial activity
beta-lactams serum cc. should exceed MIC for at least 40-60 % of dose interval
multiple dosing or continuous infusion - Cmax/MIC
- concentration-dependent antibacterial activity
aminoglycosides the higher is the cc., the better is the activity high dose once-a-day (not always) - AUC/MIC
fluoroquinolones high AUC/MIC ensure a good activity
AUC (area under the curve) – The total exposure of an antibiotic to an organism
bactericidal agents
- beta-lactams*
- glycopeptides*
- quinolones/ fluoroquinolones
- metronidazol
- rifampin
- isoniazid
- aminoglycosides
Bactericidal agents has be given in case of endocarditis, meningitis or infections in immunocompromesed patients
* Inhibit but not kill enterococci
bacteriostatic agents
- chloramphenicol
- lincosamides
- macrolides
- tetracyclines
- sulfonamides
- trimethoprim
- nitrofurantoin
- ethambutol
narrow spectrum
e.g.. G-penicilline, vancomycine, oxazolidine, lincosamied, fuzidic acid
extended spectrum
aminoglycosides, aminopenicillines, 2nd and 3rd generation cephalosporins, some fluoroquinolones, macrolides
Broad spectrum
tetracyclines, carbapenems, 4th generation fluoroquinolones, chloramphenicol, piperacilline+tazobactam
FC TCP
Consideration in choice of antimicrobial agent
- antibacterial spectrum
- site of infection
- pharmacokinetics of the antimicrobial agents
- adverse effects
- presence of renal or hepatic failure
- drug interaction (erythromycin, rifampicin)
- severity of infection
- general condition of the patient (concomitant disease, state of immune system, age, pregnancy)
- cost
Combination of antimicrobial agents (general)
Not routinely recommended
Aim:
1. To assure a synergistic effect
penicillins + aminoglycosides
sulfonamides + trimethoprim
- To extend the antibacterial spectrum
- To prevent the development of resistance
e.g. . Ps. Aeruginosa, acinetobacter infection
antimycobacterial agents
Postantibiotic effect
• Reflects the time required for bacteria to return to logarithmic growth
• Proposed mechanims:
– slow recovery after reversible non lethal damage of cell structures
– persistence of the drug at the binding site or within the periplasmic space
– the need to synthesize new enzymes before growth
• PAE is quite common in the case of G+ bacterias
• Agents with relatively long PAE (≥ 1.5 hours) against G – bacterias (not very common):
– aminoglycosides
– carbapenems
– quinolones/fluoroquinolones – rifampin
– tetracyclines
In vivo PAE is longer than the in vitro onev
Der PAE beruht darauf, dass der Schlüssel in der Bindungsstelle „klemmt“. Das führt zu einer langanhaltenden Funktionsstörung im bakteriellen Stoffwechsel, die auch dann noch anhält, wenn kein antibiotischer Wirkstoff mehr in der Umgebung vorhanden ist.
Unter PAE versteht man die in Stunden/Minuten gemessene Fortdauer der antibakteriellen Wirkung eines Antibiotikums nach Absinken unter die minimale Hemmkonzentration (MHK/MIC) bzw. auf nicht mehr messbare Werte in der Umgebung des Erregers
Base penicillins
Penicillin G and V (penamecillin)
Streptococcus species(a) enterococci (a) listeria neisseria meningitidis many anaerobes (not bacteriodes fragilis)(b) spirochetes actinomyces Erysipelothrix spp. Pasteurella multocida (b) S. pyogens T. pallidum
a- altered PBP many
b- ß-lactamase production many
Antistaphylococcal penicillins
methicillin Oxacillin Flucloxacillin Cloxacillin dicloxacillin nafeillin
indicated only for non-methilicillin-resistant strains of staph. aureus and epidermidis
lack activity against Listeria monocytogenes and Enterococcus ssp.
aminopenicillins
Ampicillin (+sulbactam)
Amoxicillin (+clavulanic acid)
extends spectrum of penicillins to include: sensitive strains of enterobacteriaccae (b), escherichia coli, proteus mirabilis, salmonella, shigella haemophilus influenzae (b) helicobacter pylori
Superior to penicillin for treatment of:
Listeria monocytogenes
sensitive enteropcocci
amoxicillin is most active of all oral ß-lactams against penicillin-resistant Streptococcus pneumoniae
carboxypenicillins
Carbenicillin
Ticarcillin
less active than ampicillin against Streptococcus species, enterococcus faecalis Klebsiella Listeria monocytogenes
activity against Pseudomonas aerigunosa is inferior to that of mezlocillin and piperacillin
ureidopenicillins
Piperacillin (+tazobactam)
Mezlocillin
extends spectrum of ampicillin to include Pseudomonasnaerigunosa (d)
Enterobacteriaceae (b)
Bacteriodes ssp. (b)
d- active efflux pump in some strains
Antipseudomonal penicillins
carboxy- and ureidopenicillins
