Antibiotico Terapia Racional

General Concepts of Antibiotics

Antibiotics are administered when the body's defense system could not control bacterial infection. This happens when there is a loss of balance or homeostasis.

General Considerations

 Minimum inhibitory concentration (MIC) is the lowest concentration of antibiotic that prevents bacterial growth.

 Post-antibiotic effect (PAE) consists in the persistent suppression of bacterial growth after a brief exposure to the antibiotic with concentrations near or below their MIC. The fluoroquinolones exert a faster bactericidal action and longer PAE.

 The oral route is always preferred as long as the patient's life is not at risk considering that absorption may be impaired by multiple causes such as poor intestinal perfusion, paralytic ileus, concurrent administration of antacids drugs, etc.

 Antibiotics with increased binding to plasma proteins (some beta-lactam) do not reach a good volume of distribution because they could not go through the capillary pores; only those antibiotics that are free in plasma would pass.

 The greater the proportion of blood vessels with respect to the area of irrigated tissue, the greater the diffusion through tissue. The skin is a tissue with a wide surface and poorly perfused, thus most antibiotics achieve low concentrations but enough to control pyodermas.

 There are antibiotics (fluoroquinolones, macrolides and rifampicin) that are distributed both in the intra- and extracellular fluid generating a tissue concentration above or equal to that in plasma. Moreover antibiotics, such as azithromycin, achieve intracellular and tissue levels much higher than plasmatic concentrations.

 Fluoroquinolones have equal bactericidal action in acute and chronic infections, thus their activity does not depend on the rate of bacterial growth.

 Conversely, beta lactams have better bactericidal action in recent infections where bacterial growth is fast. Once infection is established and bacterial growth rate decreased, the bactericidal effect of beta lactams decreases.

 It is important to take into account the route of elimination of the antibiotic administered since impaired renal or hepatic function could prolong the half-life of the antibiotic and cause toxicity.

 Those antibiotics highly bound to plasma proteins arrive in a very low concentration to tissues, nevertheless, often enough to control the infection (e.g., cephalexin).

Antibacterials Are Classified into Two Main Groups

 Bacteriostatic are those agents that temporarily inhibit bacterial growth and their effectiveness depends on the immune status of the patient.

 Bactericidal: these are drugs that cause bacterial death and are of choice, particularly in cases of reduced immunocompetence.

The latter group is subdivided into:

 Time-dependent antibiotics, such as cephalosporins and penicillins, whose bactericidal action is slow and therefore the drug concentration must be maintained above its MIC during dosing intervals to be effective. In this case, the best response is not achieved with high doses, but mainly with a greater frequency of administration.

 Concentration-dependent antibiotics, such as fluoroquinolones and aminoglycosides, where the bactericidal effect depends on the peak concentration achieved. In this case, the higher the doses better the bactericidal effect.

Characteristics Required by an Antibiotic for Dermatological Use

 Effective against Staphylococcus sp.

 Reduced spectrum

 Good bioavailability

 Good volume of distribution

 Low toxicity

 Bactericide

 Low potential for resistance induction

 Simple administration

Treatment Duration

Frequently, there are controversies between veterinary dermatologists about the duration of antimicrobial treatment in different pyodermas. In general, any appreciation on the subject is only empirical because many factors affect the duration of therapy, such as the immune status of the patient, the severity of the infection, the kind of germ, the extent and depth of the affected area, etc. Therefore, it is the evolution of the clinical picture that defines the duration of antibiotic therapy.

Thus, according to the experience of different dermatologists around the world in superficial pyoderma, the duration of treatment is estimated at 14 to 21 days and for deep pyoderma at 21 to 30 days. Nevertheless, if we use the clinical cure as the main parameter to set the duration of treatment, then it is best to continue the administration of the antibiotic (after clinical cure) for a minimum of 7 days for superficial pyoderma and a minimum of 14 days for the deep.

The duration of antimicrobial therapy for a given patient depends on the extent of the affected area, the depth of the lesion and the chronicity of infection.

Dosage and Frequency of Administration

While the dose and dosing interval are determined according to the classical pharmacokinetic parameters (plasma concentration, elimination half-life, volume of distribution, hepatic and renal clearance, percentage bounding to plasma proteins and bioavailability after oral administration), in practice both are set empirically.

Choice of Antibiotics in Superficial Pyoderma

Classified as follows:

1.  First-line antibiotics: first-generation cephalosporins, amoxicillin-clavulanic acid, lincomycin, clindamycin, erythromycin, trimethoprim-sulfamethoxazole.

2.  Second-line antibiotics: third-generation cephalosporins, doxycycline, quinolones, rifampin, chloramphenicol.

3.  Third-line antibiotics: fourth-generation cephalosporins, linezolid, imipenem and vancomycin.