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Antibiotics: Classification, pharmacokinetics and adverse effects

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General characteristics

  • Bacteriostatic
  • Bactericidal
  • Spectrum of activity:
    microbes susceptible to the specific mechanism of action of a certain antibiotic.
  • Resistance
  • Pharmacokinetics:
    the dose interval (usually 2 - 3 times/day) is determined by type of administration (oral, IV, IM, etc.), metabolism, excretion and elimination half-life.
  • Adverse effects:
    toxic, biological or allergic adverse effects may occur.
    Antibiotics very frequently (in up to 15 % of cases) cause adverse effects; serious adverse effects, however, occur only rarely!
Minimum inhibitory concentration = MIC
  • Minimum concentration required to inhibit microbial activity
Minimum bactericidal concentration = MBC
  • Minimum concentration required to kill 99.9 % of microbes
IMPORTANT: microbes that are actually covered by the spectrum of activity of a certain antibiotic occasionally may also be resistant.
If the MIC exceeds the upper limit of concentration, the microbe is considered resistant.
The selection of resistant strains leads to an increasingly weak effect of antibiotics that are usually employed (see problems due to MRSA (methicillin-resistant staphylococcus aureus)).

Oral penicillins (e.g. penicillin V, propicillin)

-narrow spectrum of activity, gram-positive pathogens only
+covers several gram-positive anaerobic pathogens
+effective in 90 % of odontogenic aerobic/anaerobic mixed infection
+very well tolerated by patients, broad therapeutic range; may also be used during pregnancy and lactation and in children

Properties

Type of actionbactericidal
Spectrumgram-positive (including anaerobic) bacteria
IMPORTANT: penicillinase-producing staphylococci
Kineticsabsorption time: 45 minutes,
impaired absorption if taken with food,
renal elimination > 50 %
Contra-indicationsallergies
Pregnancyno signs of embryotoxicity or teratogenicity
Lactationuse only if absolutely necessary
During lactation, diarrhoea, oral fungal infection (thrush) in, or sensitisation of, the infant may occur.
Adverse effectsgastro-intestinal disorders, nausea, vomiting, diarrhoea, flatulence, dry mouth, hypersensitivity reactions
Interactionscontraceptives
Indicationodontogenic infection

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The most frequent manifestation of an allergic reaction to the penicillins is the appearance of exanthematous lesions, small, circumscribed erythematous spots on the whole body, with a prevalence on the trunk.
A painless swelling of the lips occurs rather more rarely; it may result in Quincke's oedema which may be lethal (possible asphyxia).

Aminopenicillins (e.g. amoxicillin)

+range of action similar to penicillin V, plus gram-negative bacteria
-clearly less effective than penicillin V in the gram-positive spectrum
+effective against infection with penicillinase-producing staphylococci and bacteroides spp. in combination with clavulanic acid

Properties

Type of actionbactericidal
Spectrumlike penicillin V,
plus gram-negative pathogens; in combination with clavulanic acid also effective against penicillinase-producing pathogens
Kineticsabsorption time: complete absorption within 2 hours,
regardless of meals,
renale elimination 30 %
Contra-indicationsallergies
Pregnancyas with penicillin V;
if administered in combination with Augmentin: use only if absolutely necessary
Lactationuse only if absolutely necessary
Adverse effectsgastro-intestinal disorders as with penicillin V;
always consider possibility of pseudomembranous colitis should diarrhoea persist!
- discontinue medication if this is the case;
toxic ampicillin-induced exanthemata rarely occur (mainly with Coxsackie viral infection or infectious mononucleosis).
dry mouth, changes in blood parameters; superinfection caused by resistant germs in case of prolonged or repeated administration.
Increased inhibition of thrombocyte aggregation results in an increased risk of haemorrhage if acetylsalicylic acid (ASS) is administered.
IMPORTANT: pseudomembranous colitis
Interactionscontraceptives, ASS
Indicationmixed infection, if penicillin V has no effect;
in case of suspected infection with staphylococci

Cephalosporins (e.g. cefuroxim, cefaclor)

+good antibacterial effect against gram-positive bacteria and staphylococci
+/-varying effect against gram-negative and anaerobic bacteria.
More recent cephalosporins (cefuroxim) show good antibacterial effects although with poorer kinetic parameters (poor absorption).
+ well tolerated
+used if penicillin is contraindicated

Properties

Type of actionbactericidal
Spectrumlike penicillin V,
plus staphylococci and gram-negative bacteria
Kineticscefaclor: very good absorption;
cefuroxim: incomplete absorption,
renal renal elimination 70 - 90 %
Contra-indicationspossible cross-allergy with penicillin,
IMPORTANT: caution is advised if renal function is impaired
Pregnancystrict indication as the substance passes the placental barrier and there is still not sufficient experience as with penicillins.
No embryotoxic/teratogenic effect.
Lactationuse only if absolutely necessary
Adverse effectsgastro-intestinal disorders,
IMPORTANT: pseudomembranous colitis,
hypersensitivity reactions
Interactionscontraceptives, ASS
Indicationodontogenic infection

Macrolides (e.g. erythromycin, roxithromycin, clarithromycin)

-bacteriostatic!
- narrow spectrum, comparable with penicillin V; the more recent macrolides roxithromycin (e. g. Rulid®) and clarithromycin (e.g. Klacid®) are also effective against staphylococci
+ no known teratogenic/foetotoxic effect
-metabolised almost completely in the liver
+ used when penicillin is contra-indicated

Properties

Type of actionbacteriostatic
Spectrumlike penicillin V,
plus staphylococci
Kineticsvery good absorption of more recent macrolides,
incomplete absorption of erythromycin,
only minor renal excretion
Contra-indicationsallergies to macrolides,
impaired hepatic function,
IMPORTANT: interactions
Pregnancyuse only if absolutely necessary;
no embryotoxic/teratogenic effects
Lactationuse only if absolutely necessary; erythromycin passes into breast milk (sensitisation, diarrhoea and oral fungal infection (thrush) may occur in the infant), roxithromycin does not pass into the milk and is, therefore, the drug of choice from the macrolide group during lactation.
Adverse effectsgastro-intestinal disorders,
IMPORTANT: pseudomembranous colitis,
hypersensitivity reactions,
increase in liver enzymes
Interactions the effects of carbamazepine, digoxin and theophylline are potentiated;
life-threatening cardiac arrhythmia may be caused if combined with astemizol or terfenadine;
(astemizol/terfenadine are antihistamines and used in the treatment of allergic symptoms)
the effects of coumarin-type anticoagulants are intensified
Indicationsecond choice in odontogenic infections

Lincosamines (e.g. clindamycin)

+/-bacteriostatic; bactericidal effect depends on the dose
+good activity in the gram-positive range + gram-positive and gram-negative anaerobes and penicillinase-producing pathogens
+pass well through tissue, high concentration of the active substance in bone
+used when penicillin is contra-indicated

Properties

Type of actionbacteriostatic if 300 mg are administered 3 times a day;
bactericidal if 600 mg are administered 3 times a day
Spectrumlike penicillin V,
plus penicillinase-producing pathogens
Kineticsabsorption up to 75 % regardless of meals, peak blood levels after 45 - 60 minutes if taken without food, and after up to 2 hours if taken with food
Contra-indicationsallergies to lincosamines,
Crohn's disease,
ulcerative colitis,
myasthenia gravis
Pregnancycontra-indicated
There is no data long-term data available for pregnancy and lactation.
So far, there is no evidence for embryotoxicity/teratogenicity in humans.
Lactationcontra-indicated
Adverse effectsgastro-intestinal disorders
Very rarely hypersensitivity reactions.
Serious adverse effects, however, are very rare (pseudomembranous colitis).
IMPORTANT: pseudomembranous colitis,
hypersensitivity reactions
Interactionssubstances inducing neuromuscular blockade
Neuromuscular transmission disorders are intensified.
Interactions with antiepileptic drugs, benzodiazepines, etc.
Indicationdrug of choice in odontogenic infections
It is particularly indicated for osteitis/osteomyelitis/infected osteoradionecrosis (IORN) as very favourable levels of it are found in bone.

Nitroimidazoles (metronidazole)

+bactericidal
+/-no good activity against aerobes, good activity against anaerobes
- mutagenic/carcinogic in animal tests
+
good combination with penicillin due to the microbial spectra complementing each other
-
strictly no alcohol because of possible intolerance

Properties

Type of actionbactericidal
Spectrumespecially anaerobes
Kineticsmainly renal excretion;
absorption time of up to 2 hours if taken with food
Contra-indicationsallergies to nitroimidazoles,
serious damage to liver,
diseases of the central or peripheral nervous systems,
, neuromuscular transmission disorders are intensified!
Haematopoietic disorders!
Pregnancycontra-indicated during the first three months
Lactationcontra-indicated,
high concentration in breast milk
Adverse effectsgastro-intestinal disorders,
hypersensitivity reactions,
disorders of CNS/peripheral nervous system,
possible carcinogenic effect
Interactionseffect of coumarin-type anticoagulants may be intensified;
risk of haemorrhage is increased during anticoagulant treatment.
Indicationinflammatory periodontopathy

Overview

Group Substance Trade name, e.g. Daily dose
oral penicillins penicillin V
propicillin
Isocillin®
Baycillin®
3-4 x 1.2 Mega
3-4 x 1.0 Mega
amino-penicillins amoxycillin
a. + clavulanic acid
Amoxypen®
Augmentin®
3 x 0.4-1.0 g
2 x 875/125 mg
cephalosporins cefaclor
cefuroximaxetil
Panoral®
Elobact®
3 x 500 mg
2 x 500 mg
macrolides erythromycin
roxithromycin
clarithromycin
Erythrocin®
Rulid®
Klacid®
3 x 0.4-1.0 g
1 x 300 mg
2 x 250 mg
lincosamide clindamycin Clindasaar® 3 x 300-600 mg
nitromidazoles Metronidazol Clont® 2 x 500 mg

As a result from more recent studies, a dose of 2 x 600 mg up to 3 x 600 mg is recommended for clindamycin; however, this recommendation has not yet been considered in all recent statements of specialist societies.