Download Free Medical Antimicrobial therapy PowerPoint Presentation

Antimicrobial therapy PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Anaerobic Bacteria, which is titled "Antimicrobial therapy", to know about the bacterial sensitivity to specific antibiotic.

Tags : Anaerobic Bacteria, Antimicrobial therapy, bacterial sensitivity, antibiotic

Published on : Jul 01, 2021 | Views : 1402 | Downloads : 5

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Antimicrobial therapy Prof Ivo Ivić
Slide 2-

Bacterial sensitivity to specific antibiotic Determinants MIC- minimal inhibitory concentration (inhibit, but does not kill bacteria) disables visible bacterial growth in liquid media (12h) allows growth after inoculation on solid media MBC- minimal bactericidal concentrations kills all bacteria no growth after inoculation on solid media
Slide 3-

ppt slide no 3 content not found
Slide 4-

Requirements for treatment success (using conventional dosage of antibiotic) to achieve serum antibiotic concentrations above MIC to maintain this concentrations for enough long period after adminstration Time above MIC Amount of antibiotic above MIC The lower the MIC, the better the therapy The greater the AUC, the better the therapy
Slide 5-

Bacterial sensitivity to specific antibiotic – antibiogram Sensitive low MIC values for specific antibiotic conventional dosage = high probability of cure Resistant high MIC values for specific antibiotic therapeutic concentrations not achieveable by conventional or increased dosage
Slide 6-

Bacterial sensitivity to specific antibiotic – antibiogram Intermediate sensitivity MIC values increased (but not high) possibility of treatment failure Increased dosage = sometimes provides therapeutic success Example Str.pneumoniae intermediatedly penicillin sensitive Pneumonia: treatment success with increased dosage Meningitis: tretment failure even with increaed dosage
Slide 7-

Recovery from bacterial infection: relationship between antibiotic and neutrophils Antibiotic: reduces number of bacteria facilitate clearing of bacteria by neutrophils At level of 102-103bacteria/g of tissue Neutrophil clean bacteria without help of antibiotic Usualy, this point is achieved after 5 days of therapy
Slide 8-

Making decision for antibotic therapy
Slide 9-

Presence of bacterial infection? Obtain cultures including blood Observe closely Obtain cultures Patients worsens Determine probable site of infection Begin empiric therapy At day 3 Chek culture and Gram stains Negative, or Colonisation yes no Streamline antibiotic: - narrowest spectrum - fewest drug possible
Slide 10-

Making decision for antibiotic therapy: Checklist Assess the of possibility of bacterial infection Assess site of infection/pahtogen(s) involved Assess antibotic susceptibility of presumed pathogen Check data about previous antibiotic therapy/resistence Check important predisposing host factors After 3 days select drug with the narrowest antibacterial spectrum
Slide 11-

Rational selection of antibiotics Questions to be answered How broad is antibacterial spectrum of choosen antibiotic? Wether the antibiotic(s) is -cidal or -static? What are the antibotics major toxicities? How is the drug metabolised and eliminated? Is there need for dosign adjustment? What is the price of the antibiotic selected?
Slide 12-

Antibacterial spectrum of some antibiotic groups
Slide 13-

antibiotics
Slide 14-

Antibiotic groups: -lactams Aminoglycosides Glycopeptides Macrolides Ketolides Lincosamides Tetracyclines Chloramphaenicol Quinolones Oxazolidines Streptogramins Daptomycin Metrondiaziol Sulfonamides Trimetoprim Colistin
Slide 15-

β-LACTAM ANTIBIOTICS R2 side chain: -pharmacocinetics -methabolism R1 side chain: -anibacterial properties R1 R2
Slide 16-

Cephalosporins Monobactams Carbapenems Clavulanic acid Penicillins
Slide 17-

Antibacterial mechanism of β-lactams Inactivation of cell wall enzymes (PBP-s) Cessation of cell wall sythesis during active cell growth and divison Cell lysis = bactericidal effect antagonised by bacteriostatic agents
Slide 18-

Bacterial resistence mechanisms Destruction of β-lactam ring by β-lactameses penicilinases, cefalosporinases, ESBL, karbapenemases Modification of PBP-s lowered affinity for specific β-lactam antibiotic preserved cell wall syntheis
Slide 19-

Hipersensitivity to β-lactam antibiotics The most common toxicity Immediate or Delayed Anaphylactic (IgE mediated) Urticaria, angioedema Quincke Asthmatic attac Anaphylactic shock Non-anaphylactic Maculopapular rash  
Slide 20-

Hipersenitivity: Penicillins vs Cephaloporins Penicillins 1-10 % allergic reactions 1-7% cross-reactity to cephalosporins Cephalosporins 1- 3% allergic reactions rarely anaphylactic
Slide 21-

A practical approach in case of pencillin allergy Anaphylactic all β-lactams should be avoides or desensitization should be carried out Non-anaphylactic another group of β-lactams is allowed
Slide 22-

Other -lactam adverse reactions Imipenem: siezures in patients with renal dysfunction less frequent with other karbapenems Ceftriaxon: aseptic inflammation of gallbladder drug crystalisation in gallbladder Cephalosporins + aminoglycosides: nephrotoxicity Clostridium difficile diarrhoea
Slide 23-

Penicillins
Slide 24-

Penicillins Natural penicilins Aminopenicilins Penicillaze-resistent pencillins (anti-staphylococcal) Carboxypencillins and ureidopencillins (anti-pseudomonal)
Slide 25-

1.Natural penicilins (PCN) Narrow spectrum S.pygenes, S. viridans, S.pneumoniae, Neisseria meningitidis Anaerobic mouth flora Clostridium perfrigens, C.tetani, Leptosipra Short half-life: dosage 3-6 times/day Renal excretion: dose adjustment with renal funciton Preparations i.v. : PCN G i.m.: prokain PCN G, benzatin PCN G p.o.: PCN V-K
Slide 26-

2. Aminopenicillins (iv, im, po) 2a. Amoxycillin , Ampicillin Moderate spectrum: Gram-positive: Streptococci., Enterococci, Lysteria Gram-negative: E.coli, Salmonella, Haemophilus influenzae (if -lactamase sensitive) Short half life Renal excretion (unchanged)
Slide 27-

2b. Amoxycillin-clavulanate , Ampicilin-sulbactame Broader spectrum with addition of: Meticillin sensitive Staphylococcus aureus (MSSA) -lactamese producing gram-negative bacteria: Moraxella catarrhalis, H.influenzae, Enterobacteriaceae.
Slide 28-

3. Penicillase-resistant penicillins (iv, po) (meticillin sensitivity) Cloxacillin and Dicloxacillin Very narrow spectrum- Indication: MSSA, S.pyogenes (cellulitis) Ineffective against anerobes and enterobacteriaceae Short half-life Hepatal elimination (bile excretion)
Slide 29-

Carboxypenicillins and Ureidopenicillins (iv) (tikarcillin) (piperacilin) Rezisten to -lactamase of gram-negative bacteria: Pseudomonas, other enterobacteriaceae Nowdays market- only with -lactamase inhibitors: Tikarcilin-clavulanate Piperacilin-tazobactam Activity aganist: Gram-negative bactera Anaerobes (+ B.fragilis) MSSA Intrabdominal infections VAP Mixed soft tissue infections
Slide 30-

cephalosporins
Slide 31-

ppt slide no 31 content not found
Slide 32-

1st generation cephalosporins Activity: Streptoccci, MSSA, oral cavity anaerobes some CA gram negative bacilli (E.coli) Ineffective against MRSA, penicillin-resitant S.pneumoniae H.influenzae Renal excretion Do not pass blood-brain barrier Good for soft tissue infections
Slide 33-

2nd generation cephalosporins Similar to 1st generation, wider gram neg.activity H.influenzae, Neisseria sp, Moraxella catarrhalis Renal excretion Indications Uncomplicated UTI, otitis media Soft tissue infection, pelvic inflammatory disease Oral preparation (cefuroxim-axetil): low serum levels expensive
Slide 34-

3rd generation cephalosporins Activity Excellent against gram negative bacteria Nessseria sp, H.influenzae, M.catarrhalis Enterobacteriaceae Ceftazidim: the only active against Ps.aeruginosa Excelent against gram positive coccci S.pyogenes, S.viridans, other streptococci S.pneumoniae (including moderately PCN resistant strains) Poor against S.aureus and higly PCN resistant S.pneumoniae
Slide 35-

3rd generation cephalosporins Ceftriaxon- long half life: 1-2 doses/day Others: 3-4 doses/day All cross blood brain barrier Excretion Renal: for most members Ceftriaxone: hepatal (gallbladder crystals!) Indications: CA pneumonia and meningitis UTI and abdominal infections CA: Community Acquired
Slide 36-

PARENTERAL (iv, im) Cefotaxime Ceftriaxone Ceftazidime ORAL Cefexime Cefpodoxime proxetil 3rd generation cephalosporins
Slide 37-

4th generation cephalosporins (cefexime) Resistant to ESBL Wide antibacterial spectrum Similar to 3rd gen.cephalosporins plus: Ps.aeruginosa and MSSA (but not MRSA!) Indicatons Nosocomial infections (iv)
Slide 38-

5th generation cephalosporins (ceftaroline) Antibacterial spectrum Similar to 3.gen.cephalosprins(ceftriaxon) plus: MRSA and VISA (vancomyin intermdately restant SA) Indications CA pneumonia Complicated soft tissue infections
Slide 39-

Carbapenems
Slide 40-

Carbapenems Very wide antibacterial spectrum Gram negative bacteria, including: ESBL producing strains P.aeruginosa (with exception of ertapenem) Gram positive bacteria, including: MSSA (but not MRSA) Anaerobes
Slide 41-

Indications (pending results of the microbiology) Severely ill patients with nosocomial infection Severe mixed infections Carbapenems Imipenem-cilastatin Etrapenem (1dose/day, inactive against P.aeruginosa) Meropenem Doripenem Carbapenems
Slide 42-

aminoglycosides
Slide 43-

Aminoglycosides Derived form Streptomyces bacteria Bactericidal, but inactive low pH medium Post-antibotic effec: Short exposure to antibiotic Prolonged suspension of bacterial growth (despite falling of antibiotic level below MIC) The higer dose, the longer post-antibiotic effect 1 dose/day possible
Slide 44-

Activity Excellent against gram-negative bacteria Sinergy with penicillins for: S.viridans, Enterococcus, P.aeruginosa But not as monotherapy for them Renal excretion Deceased creatinin clearance Dose adjustment Aminoglycosides
Slide 45-

Toxicity Nephrotoxicity (usualy reversible) Ototxycity (usualy ireverible) Avoid aminoglicosides in: Eldery patients Renal disease Patients wit liver disase Dehidration and hypotension Combination with cephalosporins, vankomycin, clindamycin, fursemid Monitoring of serum levels is reccommended Aminoglycosides
Slide 46-

Aminoglycosides (iv, im) Gentamicin Amikacin Netilmicin Tobramicin (topical th- eye infections) Streptomycin (tularemia, plague, tb)
Slide 47-

glycopeptides Vancomycin Teicoplanin
Slide 48-

Glycopeptides Inhibt cell wall sythesis (peptidoglycan)- bactericial Long half life, postantibiotic effect 1-2 dose/day Do not cross blood-brain barrier Activity Gram positive cocci SA, S.pneumoniae, Enterococcus, etc. Renal excretion Deceased creatinin clearance Dose adjustment
Slide 49-

MR staphylococci (MRSA and koagulasa neg.) PCN highly resistant S.peumoniae Enterocci in patients with PNC allergy Clostridum difficile diarrhoea iresponsive to metronidazol (oral therapy) Limited therapeutic indications Glycopeptides
Slide 50-

Macrolides and Ketolides
Slide 51-

Macrolides and Ketolides Macrocyclic lactone ring- basic component Macrolides Erytromicin (natural antibotic) Azitromycin (iv, po) Claritromycin (po) Ketolides Telithromycin (po) Mode of action: Inhibition of protein sythesis One site of action Two sites of action Activ against macrolide resistant bacteria
Slide 52-

Toxicity (rare, safe groups) Macrolides Gastrointestinal nausea, vomiting, cramps, diarrhoea most often erithromycin Prologed QT-interval Ketolides Disturbed accomodation blured vison Severe hepatitis very rare Macrolides and Ketolides Both metabolised by cytochrome P450 Increase levels of: Short acting benzodiazepines Ritoanvir Tacrolimus, ect.
Slide 53-

Pharmacokinetics Long half life (except eritromycin): 1-2 doses/day Azithomycin: prolonged activity (5 days after cesation) Elimination by bile Azithomycin unchaneged High tissue concentrations of drugs 10-100 times of serum conc. Unsuitable to treat bacteriema/sepsis Do not cross blood brain barrier Macrolides and Ketolides
Slide 54-

Anitbacterial spectrum Vide: Gram-positive and –negative bacteria, Oral anaerobes Intracelluar bacteria Mycoplasma, Ureplasma, Chamidia, Legionella Atypical mycobacteria
Slide 55-

Treatment indications Community aquired pneumonia S.pneumoniae- increasing resistence Atypical penumonia- drugs of choice S.pyogenes increasing resistence reserve for PCN allergy Macrolides and Ketolides
Slide 56-

Treatment indications (contined) Atypical pneumonia Legionnarie disease STD (myoplasma, ureaplasma, chlamida) Atypical mycobacteria Replacement of penicillin in PCN allergy Macrolides and Ketolides
Slide 57-

clindamycin (PO, IV)
Slide 58-

Mechanism Inhibits bacterial protein synthesis the same site of action used by macrolides Excretion: liver  bile  stool Toxycity Diarrhoea reduction of sensitive flora for 14 postherapy days Cl.difficile is invoveded in 50% Clindamycin
Slide 59-

Antibacterial spectrum MSSA, S.pneumonae, S.pyogenes for PNC-allergic patients Anaerobic bacteria rising resistence of B.fragilis !! Clindamycin
Slide 60-

tetracyclines Doxycycline (po) Tigecycline (po, iv)
Slide 61-

Mechanism Inhibition bacterial protein synthesis Excretion: liver  bile  stool Toxycity Photosensitivity- rash Depistion in enemal- teeth discoloration not reccomanded under age of 8 years Beningin intracranial hypertension (headake) Tetracycline
Slide 62-

Antibacterial spectrum Very wide: gram positive and gram negative bacteria Anaerobic bacteria Intracellular bacteria Mycoplsama, Ureaplasma Chlamida Ricketssia Borellia Brucella Tetracycline Other antibotics a better ! primary indication
Slide 63-

Quinolones (or fluoroquinolones) 1.Ciprofloxacin 2.Gatifloxacin 3. Levofloxacin 4. Gemifloxacin 5. Moxifloxacin
Slide 64-

Fluorine addition: = enhanced antibacterial activity Piperazin addition = enhanced gram-negative activity Mechanism: inhibition of bacterial DNA Excretion: Kidneys: ciprofloxacin, levofloxacin, gatifloxacin Liver: gemifloxacin, moxifloxacin Quinolones = two 6-member rings
Slide 65-

Toxicity Tendinitis Articular cartilage damage qunolones are not reccommended in children A-V block (prolonoged QT interval)
Slide 66-

Ciprofloxacin : antibacterial spectrum Gram negative (wide) Primarily for Pseudomonas Other gram negative bacteria as alternative drug for prostatitis (high concentrations) Intracellular bacteria Chlamidia, Mycoplasma, Ureaplasma in case of prostatitis Gram positive (narrow) MSSA- bone infections
Slide 67-

Respiratory quinolones (levo-, gati-, gemi-, moxi-floxacin): antibacterial spectrum Ciprofloxacin spectrum, plus: S.pneumoniae (even PCN resistant) Anaerobic bacteria (gemifloxacin) Indications of respiratory quinolones: CAP (community acquired pneumonia) Mixed infections of soft tissue
Slide 68-

OUTPATIENT ORAL ANTIBOTICS
Slide 69-

Reccommendations When? higly suspected or proven bacterial infection Whom to? mild to moderately ill patients Which antibiotic? accoridng to reccommendations IDSA- Infectious Disease Society of America ESCMID- European Society of Clinical Microbiology and Infectious Disease CDC- Center for Disase prevention and Control (USA) ECDC- European CDC
Slide 70-

For instance ….. Bacterial (streptococcal) pharyngitis first choice: Penicillin VK PCN allergy: Azithromycin Community acquired pneumonia (CAP) first choice: amoxicillin or doxycycline CAP with comorbidity: levo- or moxifloxacin
Slide 71-

Antifungal agents
Slide 72-

Antifungal agents Polienes Amphotericin B Azoles Fluconazole Ketoconazole Itraconazole Posaconazle Voriconazole Caspofungin Anidulafungin Micafungin Echinocandins Flucytosine ect….. Others
Slide 73-

Modes of action of antifulgals Polyenes ergosterol binding = disrupted membrane synthesis fungicidal Azoles inhihibition of ergosterol synthesis pathway fugnistatic Echinocandins Blocking of cell wall synthesis (β-glucan) Flucytozine Imapirment of DNA and RNA synthesis
Slide 74-

Amphotericin B Azoles Echinocandins Flucytosine Modes of action of antifulgals 1 2 4 3
Slide 75-

Amphotericin B (AB)
Slide 76-

Toxicity Nephrotoxycity- usualy reversible Reduced by hidration Fever during infusion, reduced by: Slow infusion (few hours) Corticosterid premedication Phlebitis Usually CVC required
Slide 77-

Preparations: All intravenous, but: ABD- amphotericin B deoxycholate Te most nephrotoxic. The cheapest. Lipid-complex AB Less nephrotoxic. More expensive. Liposomal AB Almost non-nephrotoxic. Extremely expensive.
Slide 78-

Antifungal spectrum and indications Systemic infections (but not CNS): most Candida Aspergilus Cryptococcus Histoplasama Blastomyces Coccidiomyces Zygomyces
Slide 79-

azoles
Slide 80-

Toxicity Generaly minimal gastointesnal complaints reversible liver enzymes elevation Ketoconazole reduced libido severe hepatitis Voriconazole transient loss of vision during the first few infusions
Slide 81-

Antifungal spectrum and indications Systemic (including CNS) infections and extensive local infections (iv, po) Posaconazole and Voriconazole the widest spectrum (same as AB) very expensive Flukonazole, Itraconazole Inactive against Apergilus
Slide 82-

antiviral agents (other than anti-HIV agents ) Ribavirin Interferon-α DAA for HCV Aciklovir,valacikovir, famciklovir Ganciklovir Inhibitori neuraminidaze
Slide 83-

RIBAVIRIN Mechanism of action Interference with m-RNA Not clearly understood Toxicitiy Oral- reversible hemolytic anemia Areosol- bronchospasm Pharmacokinetics Excretion by the liver and kidney
Slide 84-

Indications RSV bronchiolitis Lasa hemorrhagic fever (Lasa virus, Arenaviridae) Chronic hepatitis C only combined with interferon-α RIBAVIRIN
Slide 85-

INTERFERON-α (INF-α ) Natural occuring antiviral cytokines Mechanism of action enhances immunological kiling of virus-infected cells poor activity against DNA viruses Pharmacokinetics (sc, im) long half-life: 2-3 doses/week Pegliated form (PegINF-α): 1 dose/week
Slide 86-

Toxicity Fever Irritability, depression, somnolece Bone marrow supression neutropenia, thrombocytopenia INTERFERONS
Slide 87-

Indications Chronic hepatitis C Combined with ribavirin Chronic hepatitis B Kaposi sarcoma (HHV-8) Condyloma acuminatum (HPV)
Slide 88-

Direct acting antivirals (DAA) for HCV-infection
Slide 89-

DAA INHIBITORs of Tableted prepartions
Slide 90-

Interaction between DAA and other drugs through CYP450 Drugs that may reduce concentrations of DAA: Antiretroviral drugs Rifampicin Anticonvulsants etc
Slide 91-

G1 HCV (naive): % of cure PegIFN + Rib 50% 48 w 8-12 w Sofosbuvir + other DAA 95-100% Duration of therapy (week)
Slide 92-

NEURAMINIDAZE INHIBITORS (oseltamivir, zanamivir) Mechanism of action inhibit enzim important for budding: release of influenza virus from infected cell effective within first 48h of disease Toxicity Zanamivir (aerosol)- bronchospasm Oseltamivir (po)- safe
Slide 93-

Indications Complicated influenza A and B with penumonia Influenza in high risk patients Therapy of uncomplicated influenza Prolonged prophylaxis (half doze)