Infectious diseases Flashcards
Selective Toxicity
An Ideal antibiotic agent targets a biological mechanism specific top the pathogen.
Easier to achieve with prokaryotes and viruses.
Minimum inhibitory concentration (MIC)
The lowest concentration of a compound that inhibits growth of the microorganism in vitro.
Minimum Bactericidal Concentration (MBC)
The lowest concentration of a compound needed to kill 99.99% of microorganisms in a colony count in vitro.
Other important pharmacokinetic factors with antibiotics
Ability to reach site of infection
Difficult areas to reach include bone, CNS, adipose.
Toxicities of Antibiotics
Allergic reactions
Idiosyncratic reactions
Pharmacogenomic reaction
Normal flora changes —> can lead to C. Diff
Bactericidal
Kills the microorganisms
Bacteriostatic
halts growth of an infection, innate immune system can then remove the pathogens
Broad Spectrum
Effective against a wide range of organisms
Extended spectrum
Agents with an intermediate range of effectiveness
Narrow spectrum
Effective against only a few organisms
Antibiotics that interfere with Cell Wall synthesis
Beta Lactams
Vancomycin
Bacitracin
Polymyxins
Antibiotics that interfere with Nucleic acid synthesis
Sulfonamides
Trimethoprim
Quinolones
Rifampin
Antibiotics that interfere with Protein synthesis
Macrolides (-mycins) Linezolid Chloramphenicol Streptogramins Tetracyclines Aminoglycosides
Cell Wall synthesis inhibitors are ____
Bactericidal
Protein and Nucleic acid synthesis inhibitors are _____
Bacteriostatic
Cell wall synthesis inhibitors prevent ________
Peptidoglycan crosslinking. This requres transpeptidase to link together D-alanine residues on murein monomers
Beta-Lactam drugs work by ____
Targeting transpeptidase. The beta-lactam ring binds transpeptidase.
Examples of Beta-lactams
Penicillins- Natural effective against Gram+ Syphillis, Extended good for Gram +/-
Cephalosporins- 5 gens, each different
Carbapenems- potent, broad spectrum
Monobactams- narrow spec, Gram - only, safe for those with allergy to Beta-lactam ring.
Beta-lactamases are a ______ that work by _____
Bacterial resistance
Opening the Beta-lactam ring
Beta-lactamase can be over come with ___
Combination therapy of strong and weak Beta-lactam.
Ex. Amoxicillin/Clavulanate
Or
Modification of antibiotic so access to ring is restricted.
Ex. Methicillin.
Glycopeptides
Cell wall inhibitors that bind to D-alanine residues on monomers.
Ex. Vancomycin
Last line treatment for MRSA
Lipopeptides
Ex. Daptomycin
Cell wall inhibitors, insert into the plasma membrane to disrupt the cell wall.
Bacitracin
Cell wall inhibitor that prevents peptidoglycan subunits from being transferred to cell surface.
Only approved for external use.
Polymyxins
Cell membrane inhibitor.
Small, positively charged peptides that disrupt structure.
Gram - only
Cannot be absorbed in GI tract due to charge.
DNA/RNA inhibitors
Broad spectrum
Direct inhibitors are Bactericidal
Indirect inhibitors are Bacteriostatic
RNA polymerase inhibitor
Rifampin
Topoisomerase inhibitor
Quinolones
DNA structure stability inhibitor
Metronidazole
Inhibitors of folic acid synthesis
Sulfonamides
Trimethoprim
Used synergistically
Protein synthesis inhibitors
Generally bacteriostatic
Either inhibit 50S or 30S ribosome
50S inhibitors
Chloramphenicol
Macrolides: Erythromycin, Clindamycin, Lincomycin
Lenzolide
30S inhibitors
Tetracyclines
Aminoglycans
Additive Combination therapy
Drugs add to each other’s efficacy in a summative manner
Ex. Beta-lactamase inhibitor + beta-lactam
Synergistic combination therapy
Drugs enhance each others efficacy greater than summative effect
Ex. Sulfonamides and trimethoprim
Antagonistic COmbination therapy
One drug impairs the efficacy of the other
Ex. Tetracyclines + Penicillins
Categories of infectious agents
Bacteria Viruses Parasites Fungi Prions
Transmission routes of infectious disease
Direct contact Fluid exchange Contamination Airborne Vector
Portals of entry
Mucosal membranes
Skin
Parenteral route (puncture)
Localized infection
Localized replication and spread of pathogen
Systemic infection
Replication and spread to blood and neurons potentially
Normal Host defenses
Skin Mucous membranes Resp tract GI tract UG tract Eyes
Host factors
Influence the course of infection: Non-specific immune response Immune status Genetics Age Nutritional status Hormones Personal Habits Fever Microbiome
Anti-viral effect of IFN
Virus infects cell and produces viral DNA, induces interferon synthesis, interferon is secreted.
Antiviral state is induced by binding of interferon to receptor on cell surface.
INTERFERON INDUCTION
EIF-2alpha Protein Kinase: inhibits initiation of mRNA translation
Oligo-adenylate synthase: activates RNSase L, leading to degradation of mRNA and tRNA.
Common types of vaccines
Inactivated pathogen
Live, attenuated
Subunit, purified antigen
Toxoid
What test delineates Staph and Strep?
Catalase test
Characteristics of a Gram-positive infection
Bullous impetigo Draining sinus tracts Erythema Fever Murmur if endocarditis Petechiae is TSS present Superficial abscesses Warmth
Streptococci
Gram positive cocci
Forms chains of cocci
Catalase negative
Ex. S. Pneumoniae, pyogenes, agalactaie, viridans
Staphylococci
Gram positive cocci
Catalase positive
S. Aureus and others
S. Aureus is Coagulase positive
Staph. Aureus diseases
Wound infection food poisoning Scalded skin syndrome TSS Endocarditis, osteomyelitis, pneumonia, brain abscesses, meningitis, and bacteremia
MRSA
Methicillin resistant staph aureus
Staph aureus virulence factors
Adhesins exotoxins- enterotoxins, TSS toxin, Exfoliative toxins Superantigens Biofilms Beta-lactamase
Conjugation
One bacteria uses a sex pili to inject part of a resistance plasmid into another
Transformation
DNA from one bacteria is lysed and incorporated into the genome of another bacteria that picks it up
Transduction
Bacteria forms bacteriophage, which injects resistance genes into new bacteria cells.
Biofilms
Aggregates of bacteria
Extremely resistance to antibiotics
Resistant to phagocytosis
Gram positive bacilli
Clostridia Bacillus Listeria Erysipelothrix Corynebacterium Mycobacteria
Can be differentiated by catalase, fermentation, urease/gelatinase, and hemolysis
Spore forming Gram + Baccilli
Clostridia
Bacillus
Anaerobic Gram + baccilli
Clostridia
Can cause abscesses and life threatening infections
Ex. C. Diff, C. Perfringens (gas gangrene)
Gram negative cocci
Neisseria
Moraxella
Appropriate culture medium for GNC
Blood agar
Chocolate agar
Thayer-Martin agar(selective for neisseria)
Neisseria
Oxidase positive
Catalase positive (except, elongata)
N. Gonorrhea
N. Meningitidis
Gram negative bacilli
Haemophillus Aggregatibacter Actinobacillus Pasturella Enterobacteriaceae Pseudomonas Burkholderia Stenotrophomonas Acinetobacter