Basic principles of antibiotic use

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Basic principles of antibiotic use Michal Holub Department of Infectious Diseases First Faculty of Medicine Charles University and Military University Hospital, Prague

1. Is antibiotical treatment indicated based on clinical findings? Obvious bacterial infection Localized infections: buccal space abscess, vestibular abscess, retropharyngeal abscess etc. Infections with characteristic clinical findings: dental infections, celullitis, streptococcal tonsillitis, infectious mononucleosis etc.

2. Urgency of the situation? Non-urgent situation: mild infection, which does not require treatment untill the diagnosis is not established Urgent situation: the patient with suspected severe infection: Localized infection ( abscess Bacterial meningitis (brain Cavernous sinus thrombosis Cervical necrotizing fascitis Mediastinitis Sepsis

3. Have appropriate clinical specimens been obtained, examined and cultured Standard cultivation Gram stain Latex agglutination (Strep test ) Appropriate cultures anaerobic and aerobic cultures Antibiotical treatment can be modified when the pretreatment cultures become available Follow up cultures are less reliable than initial pretreatment cultures

4. What organisms are most likely to be causing the infection? Type of focal infection Epidemiologic features: hospital vs. community acquired infections, prior antibiotic use, etc. Prior culture data: surveillance cultures in immunocompromised patients

Ludwig s angina (a) This patient had painful cellulitis within the submandibular and sublingual spaces. (b) Brawny edema was present within the floor of the mouth, pushing the tongue upwards. Courtesy of University of Sheffield School of Dentistry, UK.

Dental and periodontal infections Related to poor hygiene and increasing age diabetes and hormonal disturbancies (puberty and ( pregnancy Streptococcus spp., Peptostreptococcus spp., Veillonella spp., Lactobacillus spp., Corynebacterium spp., Bacteroides spp., Prevotella spp., Actinomyces spp., Fusobacterium nucleatum

Infections of oral mucosa: gangrenous stomatitis Poor oral hygiene HIV infection, measles Smoking Fusobactrium nucleatum, Borrelia vincenti, Provotella melaninogenica Gram stain + aerobic and anaerobic

Actinomycosis - diagnosis and management Head and neck swelling Poor dentition Discharging sinuses with sulfur granules Material is cultured under anaerobic conditions Intravenous benzylpenicillin (3-6 weeks) ( months followed by oral penicillin (6-12 Alternativelly amoxicillin i.v.

Infections of salivary glands Mumps (markedly decreased incidence MMR vaccination) Bacteria (patients over 60 years, diabetes, chronic illnesses) Viruses parainfluenza virus, coxsackievirus, echovirus, Epstein-Barr virus and HIV

Clinical features and pathogenes Mumps paramyxovirus Primary bacterial parotitis Staph. aureus, Strep. pyogenes, viridans streptococci and Haemophilus influenzae HIV associated salivary gland swelling cytomegalovirus ( CMV )

5. If multiple antibiotics are available to treat pathogen, which agent would be the best? Prior antibiotic allergies Antibiotic penetration - brain abscesses etc. PH - aminoglykosides are much more effective in an alkaline medium Potential side effects - chloramphenicol occurrence of aplasia Bactericidal (bc) vs. bacteriostatic agents - in lifetheatening infections or in immunocompromised patients bc antibiotics are necessary

6. Is an antibiotic combination appropriate? Synergism - one antibiotic enhances the activity of another (measured by time killing curves) - serial inhibition of microbial growth - one antibiotic enhances the penetration of another (penicillin and ( aminoglycoside Broad spectrum of activity in sepsis of unclear etiology Infection due to multiple organisms orocervical abscess

Disadvantages of multiple antibiotics Risk of drug sensitivity or toxicity Risk of colonization with resistant organism ( tetracyclin Possibility of antagonism (i.e. penicillin and Higher cost False sense of security: the use of multiple agents to cover all organisms is not possible and may be associated with complications

7. Are there special considerations related to host factors? Genetic factors Pregnancy and lactation: A. antibiotics considered safe - penicillins, cephalosporins, erytromycin base; B. antibiotics to be used with caution - aminoglykosides, vancomycin, clindamycin, imipenem-cilastatin and cotrimoxazole Renal and liver functions

8. What are important adverse reactions? Clindamycin Clostridium difficile-mediated diarrhea, allergic reaction Penicillin V (phenoxymethylpenicillin) mild to serious alleric reaction Amoxicilllin-clavulanate allergy, diarrhea, hepatotoxicity, C. difficile-mediated diarrhea, maculopapular rash with infectious mononucleosis and chronic lymphocytic leukemia

9. What is the appropriate dose? Generic name phenoxymethylpenicillin amoxicillin-clavulanate cefuroxime Oral regimen 500mg q6h 625mg q8h 500mg q12h Intravenous regimen 1.2g q4h* 1,2g q8h 750mg q8h metronidazol clindamycin fluconazol 250mg q12h 300mg q6h 100mg q12h 400mg q8h 450mg q8h 200mg q12h * benzylpenicillin

References Reese RE, Betts RF. A Practical Approach to Infectious Diseases. 3rd edition. Boston, Little, Brown & Company 1991 Reese RE, Betts RF, Gumustop B. Handbook of Antibiotics. 3rd edition. Philadelphia. Lippincott Williams & Wilkins 2000 Cohen J, Powderly WG (eds.). Infectious Diseases. 2nd edition. Edinbourg, Mosby 2004 European Antimicrobial Resistance Surveillance System (EAARS). EAARS Annual Reports 2001 and 2005 Mandell GL, Bennett JE, Dolin R (eds.). Principles and Practice of Infectious Diseases, 6th edition. Philadelphia, Elsevier 2005 The Sanford Guide to Antimicrobial Therapy 2016, 46th edition. Sperryville, Antimicrobial Therapy Inc. 2016