 Resistant = NOT inhibited

 Sensitive = inhibited
 Chemotherapeutic agent = drug to treat any illness or dz
 Antimicrobial agent = substance interferes w/ proliferation of microorganisms
o viruses, bacteria, protozoan, fungi, etc.
 Abx = compound w/ antimicrobial activity
o sources is “natural” living organisms
o Soil microorganisms - Streptomyces
 Bacteriostatic = inhibit growth
o Need functioning immune system
o Slow growth of pathogen – slows dz progression – allows immune system to eliminate pathogen
o Regrowth
 Bacteriocidal = kills – need in rapidly lethal infections
o Immune suppressed pt
o Irreversible lethal
 Narrow spectrum = abx ONLY affect certain classes
o Directed
o Gram (+), Gram (-), anaerobes, or mycobacteria
 Broad spectrum = successful against BOTH gram (+) & gram (-)  preferable if….
o Empiric therapy needed – life-threatening infection
o Prophylaxis prior to surgery
 Poor selective toxicity = common target b/w microbe & host
o Agent harmful to BOTH pt & microbe
o More similar drug target is same to target in human host  poorer the selective toxicity
o Bad target = cell membranes = BOTH bacteria & humans have
 Agents that target membrane integrity = poorest selective toxicity = greatest potential to damage human @
therapeutic levels
 Good selective toxicity = exclusive target in microbe
o Agent well tolerated by pt but harmful to microbe
o Less similar (absent) target in human host  better the selective toxicity
o Ex: Human lack of peptidoglycan cell wall
 Penicillin = good selective toxicity
 Superinfection = treat 1 dz & new/different dz develops @ another site
o Treat pharyngitis  vaginal yeast infections
o Treat pneumonia  Clostridium difficile abx-associated pseudomembranous colitis
 Location of infection = different abxs penetrate different tissues to varying degrees
 Antimicrobial = drug interactions do occur
 Limitations to effective chemotherapy: (6)
o 1) Abscess formation
o 2) Foreign bodies
o 3) Immunosuppression
o 4) Superinfection
o 5) Location of infection
o 6) Antimicrobial-drug interactions do occur
 Chemoprophylaxis = give drugs to pt who is not infected but has increased risk for infection
o 1) Justified
 1) Animal & human bite wounds
 2) Crede procedure
 AgNO3 & erythromycin/tetracycline eye drops or salve  prevent ophthalmia neonatorum
 3) Prophylaxis against….
 Malaria
 Bacterial endocarditis
 Rheumatic heart dz (valvular abnormalities, congenital heart dz)
 Could breach mucosal surfaces  result in transient bacteremia….
o Dental manipulations
o Respiratory, gastrointestinal, urogenital procedures
 4) Surgeries  crossing mucosal surface that contain normal flora
 Bowel surgery
 5) Infections in immunocompromise
 Neutropenia
 HIV/AIDS
 6) Recurrent UTIs
 7) Post exposure prophylaxis
 Meningococcal meningitis dz/outbreaks
 MTB infection or exposed to TB pt
 HIV – exposed or infected
  Airborne pathogen  6 ft distance
o 2) Unjustified
 Prevent 2 bacterial pneumonia after influenza or other viral respiratory infections
 Clean surgery  not breach mucosa or site already contaminated w/ bacteria
 General surgery, plastic surgery
 Pt insists abx
o Combinational therapies = administration of 2 or more abxs in combination
o Synergism = 2 or more drugs when used together are cidal @ [ ]’s lower than that of either component used alone 
beneficial, administers lesser amts of toxic drug (1+1=32)
 Aminoglycoside
 Penicillin
o Additive effect = 1 or 2 drugs are toxic, then decreasing [ ] of each by 50% beneficial (1+1=2)
 Limited form of synergy w/ limited clinical usefulness
o Antagonism = activity reduction of 1 or both components of therapy when both present (1+1=0.5)
 Due to….
 Competition – binding site
o Erythromycin & chloramphenicol
 Drug/drug interaction – opposing effects
o Tetracycline & penicillin
 Tetracycline = protein synthesis inhibitor – slows growth of bacterium plus
production of peptidoglycan – reducing target (cell wall) of penicillin
o Indifference = combined action same as w/ either component alone (1+1=1)
 Not clinically useful – not used in clinic
 Abx combinations are indifferent
o Mechanisms of Resistance of Antimicrobial Agents = multiple ways bacteria to avoid adverse effects of abxs
 1) PBPs (penicillin binding proteins)  (B-lactams) penicillins
 2) DNA gyrase  fluoroquinolones
 3) Dihydrofolate reductase  trimethoprim
 3) D-alanine replaced w/ lactic acid in murein side chain  vancomycin resistance
o Prevent access of drug to target
 Drug efflux pump  drug excretion > drug entrance
 Reduced drug permeability  phospholipid changes  changes cell reduce rate @ which drug enters cell
o Inactivation of drug – destruction of agent
 B-lactamase = penicillinase
 Organisms elaborate B-lactamases – cleave B-lactam ring – B-lactam ring abxs:
 Penicillins
 Cephalosporins
 B-lactamase inhibitors developed to inhibit B-lactamases
 Clavulonic acid
 Tacobactam
 Sulbactam
 4 major classes of resistance mechanisms to B-lactam abxs
 1) Penicillinases
 2) Cephalosporinases – AmpC-type
 3) extended-spectrum B-lactamases – ESBLs
 4) Carbapenemases
o 6 abx resistant bacteria – urgent by CDC
 1) MRSA = methicillin-resistant Staphylococcus aureus
 2) CRE = carabapenum-resistant Enterobacteriaceae
 3) ESBL = extended-spectrum B-lactamases – producing Enterobacteriacea
 4) VRE = vancomycin-resistant enterococci
 5) Multi-drug resistant Pseudomonas
 6) Multi-drug resistant Acinetobacter
o Tolerance = resistance mechanism  evasion of killing
 NO change in MIC but MBC increase factor 32
 MBC:MIC = ≥ 32:1
 ALL studies restricted to B-lactam abx – other cell wall agents
 Rare
 Evasion of killing by:
 Phenotypic = depress bacterial growth rate
 Genotypic = depress production of murein (peptidoglycan) hydrolases – or other key enzymes of
cell wall synthesis
o Epidemiology = study of distribution of determinants of dz & injury
o Epidemiologic triad  pattern of interaction b/w  dz occurrence can be blocked by intersecting any of these 3 sides
 1) host
 2) agent
 3) environment
o Reservoir of infection (aka source of agent) = continual source of infection
 Living Reservoirs
 Human reservoirs of infection
o People who have dz
o People who are carriers of pathogenic microorganisms
 Zoonoses = dz that affect wild & domestic animals & can be transmitted to humans
 Nonliving Reservoirs
 Soil  fungi, C. botulinum, C. tetani
 Water  V. cholerae, S. typhi, protozoans, algae
 Improperly prepared or stored foods (salmonellosis)