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antibiotic resistance
antibiotics are selective agents, because they kill susceptible bacteria, they select for resistant mutants, it’s a threat worldwide.
Overuse of antibiotics
high rates of resistance are attributed to overuse.
human medicine
agriculture: use of subtherapeutic antibiotics in animals
emerging antibiotic resistant bacterial pathogens
MRSA, VMRSA
carbapenem - resistant klebsiella pneumonia
multi drug resistant uropathogenic e.coli (UPEC)
NDM1 - positive bacteria
K. pneumoniae
an encapsulated gram negative bacterium
lives in gut on humans and animals ( not causing problems )
opportunistic pathogen
if gains access to extra intestinal sites (bloodstream, lungs) infections can become deadly
Nosocomial pathogen
hospital acquired pathogen
carbapenems
antibiotics that break down bacterial cell walls
transposons
genes for antibiotic resistance acquired via the transposons delivered by bacteriophages
NDM1
new type of drug resistance
new delhi metallo beta lactamase
some NDM1 positive bacteria are resistant to most/all antibiotics
major problem in gram negative pathogens
major genetic element encoding multiple drug resistance genes, contained within transposons on a plasmid
carbapenem resistant
carbapenem resistant NDM1 positive klebsiella is also resistant to most disinfectants
emerging nosocomial pathogen
very contagious - transmitted patient to patient, medical worker to patient, from fomites, indwelling devices.
UPEC leading cause of urinary tract infections
cystitis
pyelonephritis
renal damage
potential systemic infections
8-65% of UPEC strains are resistant to drugs commonly used to treat these infections
selectively toxic
should kill/ inhibits microbes without damaging host
“perfect” antimicrobial drug
selectively toxic
microbial (kills microbes) rather than microbistatic (stops from replicating)
remains potential long enough to be effective
doesn’t lead to antimicrobial resistance
easily delivered to site of infections
reasonably priced
antimicrobial drug origin
mostly made by bacteria and fungi
common bacterial producers
common fungal producers
natural antibiotics
directly isolated from microbial source
semisynthetic drug
chemically modified after being isolated from natural source
synthetic drug
produced entirely by chemical reactions
narrow spectrum
used to target specific group of microb
ex only targets gram positives or only some gm+
medium spectrum
effective against some gram positives and gram negatives but not all types
broad spectrum
effective against most gram positive and gram-negative bacteria
minimum inhibitory concentration assay
incubate bacterium in presence of increasing concentrations of drug, measuring the lowest concentration of the drug resistance to inhibit bacterial growth
antibacterial drug that targets the bacterial cell wall
beta lactam
glycopeptide
polypeptide
antibacterial drug that targets protein synthesis
aminoglycosides
ampheniols
tetracyclines
antibacterial drug that targets cell membrane
polymixins
antibacterial drug that targets bacterial nucleic acids systhesis
quinolones
antibacterial drug that targets folic acid sythesis
sulfonamides
beta lactam antibiotics
penicillins
cephalosporins
(carbapenems)
glycopeptide antibiotics
vancomycin
polypeptide antibiotics
bacitracin
bacterial target
bacterial transpeptidases located in cell wall. These enzymes help build and repair peptidoglycan in the bacterial cell walls
trans peptides are easier to access in gram positives than gram negatives
original source penicillin
mold penicillium chysogeum
natural penicillin
narrow spectrum, effective against gram positives
semisynthetic penicillins
medium spectrum, also effective against some gram negative bacteria
resistant bacteria produce
beta lactamases
enzymes that break apart b lactam ring
drug development
penicillins that are resistant to some bacterial b lactamases
clavamox
amoxicillin with additional clavulanic acid
clavulanic acids inhibit activity b lactamase enzymes
medium spectrum
oxacillin and methicillin
inhibit some staphylococcal b lactamases
useful for treating s, aureus, but not for MRSA
narrow spectrum: mostly gram positives