introduction to Infectious diseases.pptx

Infectious diseases Dr. Najla Abdalmuniem Alkaruri TABLE OF CONTENTS 01 What is infection? 02 Bacterial infections 03 Revision for Antibiotics Antimicrobial Regimen 04 Selection What is infection? Infection is the invasion and multiplication of microorganisms in...

Infectious diseases Dr. Najla Abdalmuniem Alkaruri TABLE OF CONTENTS 01 What is infection? 02 Bacterial infections 03 Revision for Antibiotics Antimicrobial Regimen 04 Selection What is infection? Infection is the invasion and multiplication of microorganisms in or on body tissue that produce signs and symptoms along with an immune response. Such reproduction injures the host either by causing cellular damage from microorganism-produced toxins or intracellular multiplication or by competing with host metabolism. The host’s own immune response may increase tissue damage, which may be localized (as in infected ulcers) or systemic. The severity of the infection depends on such factors as microbial characteristics, the number of microorganisms present, and the way in which the microorganisms enter the body and spread The very young and the very old are most susceptible to infections. The inflammatory response The body reacts to microbial invasion by producing an inflammatory response. The five classic signs and symptoms of inflammation are as follows: Redness—Caused by dilation of arterioles and increased circulation to the site Pain—Results from stimulation of pain receptors by swollen tissue Heat—Caused by local vasodilation, fluid leakage into the interstitial spaces, and increased blood flow to the area Swelling—Caused by local vasodilation, leakage of fluid into interstitial spaces Loss of function—Results primarily from pain and edema Other manifestations: fever, malaise, nausea, vomiting, and purulent discharge from wounds.  Types of infection Microorganisms responsible for infectious diseases include: Bacteria Viruses DNA viruses Gram -ve and Gram +ve Micro- RNA viruses organis ms Parasites Fungi Protozoae and yeasts and helminths molds Bacterial infections  Classification of bacreria  Bacteria are classified by : Shape. Spherical bacterial cells are called cocci; rod-shaped bacteria, bacilli; and spiral-shaped bacteria, spirilla. Gram staining (gram-positive, gram-negative, or acid-fast bacteria); Oxygen consumption; aerobic, nonaerobic Motility (motile or nonmotile bacteria); Encapsulation (encapsulated or nonencapsulated bacteria); Spores forming (sporulating or nonsporulating bacteria). Revision for Antibiotics  Fleming and Penicillin The first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology in 1928 at St. Mary's Hospital in London. Antimicrobials VS Antibiotics Antibiotic: Chemical produced by a microorganism that kills or inhibits the growth of another microorganism Antimicrobial agent: Chemical that kills or inhibits the growth of microorganisms  Classification of antibiotics based on : Mode of action Spectrum Bacteriostatic & of activity bactericidal Narrow spectrum Mechanis Broad spectrum, …. m of Antibioti action cs structure Beta-lactams Tetracyclines Natural or fluroquinolones synthetic Classification of antibiotics based on mechanism of action Classification of antibiotics based on mechanism of action Cell wall synthesis Nucleic acid synthesis inhibitors inhibitors penicillins Quinolines rifamycins Carbapenems cephalosporins Folate synthesis monobactams inhibitors vancomycin Sulphonamides Protein synthesis Trimethoprin inhibitors Aminoglycoside Others Tetracyclines Metronidazole Macrolides Daptomicyn Chloramphenicol Fosfomycin Clindamicin Tigecycline Linezolid Classification of antibiotics based on Mode of action Bactericidal Bacteriostatic Those target cell wall Those target protein (penicillins, synthesis cephalosporins) or cell (Macrolides, tetracyclines, membrane (polymyxins) lincosamides) or enzymes (rifamycin,quinolones, NB. Except aminoglycosides sulphonamides) which is bactericidal Classification of antibiotics based on Spectrum of activity Narrow Spectrum: eg. Penicillin G streptococcus Broad Spectrum eg. Amoxicillin/clavulanic acid. tetracyclines and chloramphenicol Extended Spectrum eg.iperacillin, ticarcillin High Extended Spectrum eg piperacillin/tazobactam No antibiotic is effective against all microbes  Cephalosporins First Third generation generation cefazolin, Ceftriaxone cefalexin, cefotaxime cefradine, Cefixime cefadroxil cefoperazone Cefapirin Ceftazidime cephalothin Second Fourth generation generation Cefuroxime cefepime cefpodoxime Fourth Cefoxitin generation Cefotitan ceftaroline Cefaclor cefprozil  Cephalosporins skin and soft tissue infections and the prevention of hospital- acquired surgical infectionsn, pneumonia, meningitis, and other infections. First-generation cephalosporins are active predominantly against Gram-positiveSuccessive generations of cephalosporins have increased activity against Gram-negative bacteria the cross-reactivity rate with penicillin is about 4-10%(more in 1 st generation and lesswith 3rd and 4th)  Aminoglycoside Amikacin Genamicin Topramicin Streptomycin Effective against mainly gram –ve and psudomonas and some gram +ve , ESPBL (extended spectrum betalacamase producers )  Macrolides Azithromycin Clarithromycin Erythromycin pneumonia chronic obstructive pulmonary disorder sinusitis tonsillitis skin infections ear infections chlamydial infections Helicobacter pylori infections  Tetracyclines Tetracycline Doxycycline Minocycline Tigecycline (a member of a new class of tetracycline-related antimicrobial agents, the glycylcyclines,) Variety of Gram +ve and –ve bacteria skin infections, such as acne chlamydial infections syphilis traveler’s diarrhea  Fluoroquinolones ofloxacin ciprofloxacin Levofloxacin respiratory quinolone Moxifloxacin respiratory quinolone Gemifloxacin respiratory quinolone -ve moderate +ve bacterial bronchitis pneumonia sinusitis UTIs septicemia joint and bone infections  Folate inhibitors Sulfonamides Trimesoprin Glycopeptide Vancomycin Linezolid Gram +ve and MRSA and have anti clostridium difficile Others Daptomycin MRSA Clindamycin Gm +ve., MRSA, anti-anaerobes Metronidazoles anti-anaerobes and protozoal Anti-pseudomonal activity 3rd generation: Ceftazidime. 4th generation: Cefipime Fluoroquinolones : (Ciprofloxacin, Levo-) Piperacillin/tazobactam Carbapenems : (except ertapenem). Aminoglycosides (Tobramycin and Gentamicin). Tigecycline. Anti-MRSA Anti-anaerobes Metronidazole the most effective antimicrobials against anaerobic organisms carbapenems (imipenem, meropenem and ertapenem), clindamycin. penicillins with a beta-lactamase inhibitor combinations ○ Amoxicillin or ticarcillin plus clavulanate, ○ ampicillin plus sulbactam, and ○ piperacillin plus tazobactam), chloramphenicol, tigecycline Antibiotics Resistance Antimicrobial Regimen Selection  Systematic Approach for Selection of Antimicrobials 0 infection 0 Selection of presumptive Confirm the presence of therapy considering 1 3 every infected site Careful history and physical Host factors Signs and symptoms Drug factors Predisposing factors 0 Identification pathogen of the 0 Monitor therapeutic response 2 Collection of infected 4 Clinical assessment material Laboratory tests Stains Assessment of Serologies therapeutic failure Culture and sensitivity 1. Confirm the presence of infection Fever is defined as a controlled elevation of body temperature above the normal range of 36.7 to 37.0°C (98.1 to 98.6°F) (measured orally). White blood cell (WBC) elevated counts (leukocytosis) because of the mobilization of granulocytes and/or lymphocytes to destroy invading microbes. Normal values for WBC counts is between 4,000 and 10,000/mm3. ○ Bacterial infections are associated with elevated granulocyte counts (neutro phils, basophils), ○ Relative lymphocytosis, even with normal or slightly elevated total WBC counts, is generally associated with tuberculosis and viral or fungal infections. Pain and inflammation swelling, erythema, tenderness apparent only if the infection is superficial 2. Identification of the pathogen Before the institution of antimicrobial therapy. First, a Gram stain of the material may reveal bacteria, or an acid-fast stain may detect mycobacteria or actinomycetes. Specimens cultures should be performed in the acutely ill, febrile patient 3. Selection of therapy Impiric (presumptive) therapy Before identification of the pathogen It is usually broad spectrum Definitive (Target) therapy pathogen is identified Narrow specrum Prophylactic therapy To prevent initial infectionon recurrence before infection  In choosing AB therapy factors must be considered, including the severity and acuity of the disease host factors, Drug factors 3. Selection of therapy  host factors  Drug factors Age of patient Spectrum of activity Location of infection Tissue penetration Pregnancy Dosing Metabolic abnormalities pharmacokinetic Renal and hepatic function pharmacodynamic properties Concomitant drug therapy ADR potential Concomitant disease states Interactions potential Adherance potential Cost When selecting antimicrobial regimens, local susceptibility data should be considered whenever possible (local antibiogram) Combination therapy Advantages: Disadvantages : Broadening the spectrum of Increased cost coverage Greater toxicity Synergism eg. endocarditis ADRs ?? Eg. Gentamicn & vancomycin and nephrotoxicity Source control  Antibiotics are unlikely to be effective in presence of source of infection ,it must be removed  Source control Refers to the process involve: Removal of prosthetic materials eg. Catheters, joints Removal of Infected and necrotized tissues (depridment) Drainage of abscesses 4. Monitoring therapeutic response Monitoring through 1. Culture and sensitivity reports from specimens collected 2. Use of agents with the narrowest spectrum of activity against identified pathogens 3. Signs and symptoms of infection, fever, appetite, wellbeing….. 4. Parameters including white blood cell count, ESR, CRP, … 5. radiologic studies as appropriate, 6. Therapeutic drug monitoring (TDM) measure the concentration of the drug in the serum to ensure efficacy and avoid toxicity 7. The route of antibiotic administration. Switch to oral therapy as soon as possible (as the patient improves) Optimization of AB therapy Failure of antimicrobial therapy Failures caused by Drug Selection 1. inappropriate selection of drug, eg. poor penetration into the site of infection eg. CNS, the eye, the prostate gland. 2. dosage, subtherapeutic dosing or route, or duration (eg. In some chronic infections like endocarditis and osteomyelitis there is a need for weeks to months) 3. Malabsorption of a drug product because of GI disease (e.g., short-bowel syndrome) 4. Drug interactions (e.g., complexation of fluoroquinolones with multivalent cations resulting in reduced absorption) 5. Accelerated drug elimination eg. during pregnancy, when more rapid clearance or larger volumes of distribution Failures Caused by Host Factors 6. Patients who are immunosuppressed 7. Lack of surgical drainage of abscesses or removal of foreign bodies and/or necrotic tissue (poor source control) Any question ?