Download Antimicrobial Agents: Sterilization, Disinfection, Antiseptics, and Mechanisms of Action and more Quizzes Microbiology in PDF only on Docsity!
Sterilization
killing or removal of all forms of microbes, including spores
heat, radiation, filtration, & chemical
TERM 2
Disinfection
DEFINITION 2
- killing of MOST infectious disease-causing microbes
primarily chemicalthese examples are for the 3 antimicrobial
methodsEx. glutaraldhyde disinfectant (& sterilant) phenol -
disinfectant hydrogen peroxide antiseptic (& disinfectant)
TERM 3
Antiseptic
DEFINITION 3
- disinfectant that is safe to use on tissues TERM 4
Categories of Infection Risk
DEFINITION 4
Critical - contact with internal fluids or tissues, such as blood
or blood vessels Semi-critical - contact with mucous
membranes or contact with broken skin Noncritical - contact
with intact skin
TERM 5
Methods of Sterilization
DEFINITION 5
High Temperature Autoclaving / moist heat Boiling (100 C)
kills vegetative bacteria, but not spores Autoclave / pressure
cooker 15 lbs. pressure / steam @ 121 C 121 C for 15-20 min.
required to kill bacterial spores Standard conditions: 15 lbs.
pressure, 15 min., 121 CDry heat / oven Hot air @ 160-180 C
for 2-3 hrs.
Additional Methods of Sterilization
Radiation Ultraviolet / @ 260-280 nm / thymine dimers surface sterilization / bench topsGamma rays / free radical formation penetration / plastics & rubber products / meats(?) Filtration (sterilization?) / 0.22-0.45 um pores retain bacteria heat labile solutions Chemical Gas sterilization / ethylene oxide plastics, surgical instruments & devicesLiquid (cold) sterilization / ex. glutaraldehyde / EPA registered surfaces & surgical instruments TERM 7
EPA Registration of Disinfectants
DEFINITION 7 High-level disinfectants kill all microorganisms, except bacterial spores. Intermediate-level disinfectants (minimal hospital- level) kill Mycobacterium tuberculosis , most other bacteria, most viruses, and most fungi, but not bacterial spores. Low-level disinfectants kill most bacteria, some viruses, and some fungi, but cannot be relied on to kill resistant microorganisms (M. tuberculosis) or bacterial spores TERM 8
Mechanisms of Action
DEFINITION 8 Disruption of cell membranes Phenol(s) / 1st disinfectant used by Lister ~ 1860 methylphenol (cresol) / EPA-registered hexachlorophene / soaps Phenol coefficient Compares activity of new disinfectant to phenol more effective than phenol have a coefficient > 1 less effective have a coefficient < 1 Alcohols 70% ethanol used to clean skin not EPA-registered disinfectant Detergents skin antiseptics TERM 9
STERLANTS & HIGH LEVEL DISINFECTANTS
COMMONLY USED IN HOSPITALS
DEFINITION 9 Ethylene oxide - gas sterilization, several drawbacks, a human carcinogen Glutaraldehydes (~2.4-3.4%) - not a carcinogen, but some adverse health effects - sterilant/disinfectant Ortho- phthalaldehyde (OPA) - Hydrogen peroxide (~7.5%) - sterilant/ disinfectant Peracetic acid (~0.2%) - sterilant Peracetic Acid-Hydrogen Peroxide mixtures - disinfectant/sterilant Hypochlorite -High Level Disinfectant TERM 10
Mechanisms of Action inactivation of microbial
proteins, nucleic acids, etc
DEFINITION 10
alkylation Glutaraldhydes & ortho-
phthalaldehyde oxidation Peracetic acid & hydrogen
peroxide halogenization Chlorine / hypochlorite / chlorine
dioxide 0.5%-1% hypochlorite is viricidal (HIV & HBV) (1/
dilution of household bleach = 0.5%) Iodine Most effective
skin antiseptic tincture of iodine / iodopohors
Major targets of antimicrobials
Cell wall synthesisProtein synthesis Nucleic acid synthesis
Cell membrane synthesisOthers
TERM 17
Inhibition of cell wall synthesis
DEFINITION 17
B-lactams - penicillin(s) & cephalosporins beta-lactam ring
essential for activity non-toxic except for hypersensitivity
reactions inhibit transpeptidation of peptidoglycan & activate
autolytic bacterial enzymes / bactericidal
TERM 18
Modifications of penicillin
DEFINITION 18
Pen G IM or IVPen VK - POVarious groups can be substituted
at R to produce new penicillins Ampicillin Amoxicillin (acid
stable, Gram- activity) (better absorption, >blood levels)
Nafcillin (methicillin, oxacillin) Cefotaxime (resistant to
B-lactamases) (a cephalosporin)
TERM 19
Common Mechanisms of Resistance to B-
lactam Antimicrobials
DEFINITION 19
bacterial B-lactamases microbial enzymes that hydrolyze
the -lactam ring bacterial exclusion prevention of entry by
porin molecules target modification mutational changes in
microbial transpeptidase(s) (PBPs) so no longer bind
antimicrobial
TERM 20
Bodyguards for Penicillins
DEFINITION 20
Ampicillin with sulbactam Amoxicillin with
clavulanate Sulbactam & clavulanate = structural analogs of
penicillinthey have little, if any, antimicrobial activity -
however they bind to bacterial -lactamase(s) & protect
ampicillin/amoxicillin from hydrolysis
Other B-lactam antimicrobials
Monobactams resistant to many -
lactamasesAzetreonam (1986) usually IV or IM (also
inhalable) useful for Enterobacteriaceae & Pseudomonas
cystic fibrosis w/ P. aeruginosa useful for penicillin-allergic
patients not effective for gram-positives (inc. MRSA & VRE)
or anaerobes (inc. gram-negatives)
TERM 22
Other B-lactam antimicrobials -continued
DEFINITION 22 Carbapenems go-to drugs for serious multi-drug resistant & polymicrobial infections very broad spectrum, except MRSA & VRE resistant to most B-lactamases usually IV & restricted to hospital usage Imipenem hydrolyzed by renal dehydropeptidase- to nephrotoxic metabolites,so used in combination with cilastatin (inhibits dehydropeptidase- Meropenem (1996) and other newer carbapenems resistant to renal DHP- TERM 23
Emergence of Carbapenem Resistance in
Enterobacteriaceae
DEFINITION 23 ( 1) Klebsiella pneumoniae (KPC extended spectrum - lactamase) **(2) New Delhi metallo-beta-lactamase (blaNDM-
- resistance to all B-lactams** (except aztreonam) 2008 - 1st reported (native of India in Sweden) 2010 15-20 countries, including US USA Jan-June 2010 3 isolates detected in USA all patients had received medical care in India also resistant to azetreonam* medical tourism ~1.7 million US residents in 2012*these isolates often only sensitive to colistin & tigecycline TERM 24
Other cell wall inhibitors (not B-
lactams)
DEFINITION 24 Vancomycin / high-molecular weight glycopeptide blocks transpeptidation of peptidoglycan (binds directly to D-alanyl-D-alanine precursor) bactericidal restricted usage MRSA & serious systemic enterococcal infections developing resistance vancomycin- resistant enterococci - VRE vancomycin-intermediate S. aureus - VISA or GISA vancomycin-resistant S. aureus - VRSABacitracin bactericidal (Gram-positives) topical only - no systemic usage / kidney toxicity usually combined with polymixin B & neomycin ( Gram- negatives) TERM 25
Mechanism of Vancomycin Resistance
DEFINITION 25
Vancomycin-resistant (VanA & VanB) strains substitute D-
lactate for D-alanine in peptide side chain of
peptidoglycan Vancomycin-resistant Substitution of D-
lactate for terminal D-alanine prevents vancomycin from
binding to peptidoglycan precursor and inhibiting cell wall
synthesis
Inhibition of Nucleic Acid
Metabolism
Quinolones (ex. ciprofloxacin) inhibits bacterial DNA gyrase activity- inhibits replication bactericidal / broad spectrum Rifampin inhibits bacterial RNA-polymerase - inhibits transcription bactericidal rapid resistance, therefore primarily usually used in combination Sulfonamides (ex. sulfamethoxazole) & Trimethoprim inhibit separate steps folic acid synthesis bacteriostatic synergistic action useful for urinary tract infections TERM 32
Alteration of cell membrane function
DEFINITION 32 Bacterial Polymixins (colistin) Fungal Polyenes (amphotericin B & nystatin) bind to ergosterol Azoles (miconazole, fluconazole, clotrimazole) inhibit ergosterol synthesis Terbinafine inhibits squalene oxidase Miscellaneous Bacterial Metronidazole primary activity against anaerobes Isonazid inhibits mycolic acid synthesis (Mycobacterium) Fungal Griseofulvin - inhibits mitosis of fungal cells (?) Echinocandins inhibits 1-4 glucan synthesis TERM 33
Primarily for MRSA &
VRE
DEFINITION 33
quinupristin/dalfopristin (Synercid) MOA: protein
synthesislinezolid (Zyvox) MOA: protein synthesis, inhibits
assembly of ribosomeDapomycin (lipopeptide) - most
frequently used MOA: disrupts membrane
structureTigecycline (glycylcycline) MOA: inhibits protein
synthesis
