Microbiology-3-Hospital Acquired Infection and Antibiotic Resistance Flashcards
What are the reasons for the high rate of hospital acquired infections?
-High density of susceptible people -Presence of the pathogen -Staff vectors -Open wounds -Inserted medical devices (IV catherters, Disruption of normal flora due to anitibiotics propholaxis/therapy)
Name the important bacterial pathogens that are multi-drug resistant?
Gram-neagtive: P.aeruginosa, E.Coli (ESBL,NDM-1), Salmonella spp, A. baumanii Gram Positive- S.aureus, S.pneuminiae, C.difficile, Enterococcus spp. Also, M.tuberculosis
Summarise some of the main approaches used to prevent the emergence of drug-resistant bacteria and nosocomial(originating in a hospital) infections?
-Better prescribing practices -infection Control -Combination Therapy -Narrow vs broad spectrum antibiotic therapy
The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-causing bacteria. A broad-spectrum antibiotic acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of bacteria.
Summarise the mechanisms of antibiotic resistance?
-Decreased drug accumulation -Altered metabolism -Inactivation of antibiotic -Altered target site
DIAA
How does an Altered metabolism protect a resistant bacteria against Antibiotics?
Re-engineer the metabolic pathways so you bypass the step that the antibiotic interferes with.
Increased production of enzyme substrate can be used to outcompete antibiotic inhibitor
How does an Inactivation of an antibiotic protect a resistant bacteria against Antibiotics?
Enzymatic degradation or alteration, rendering antibiotic ineffective.
How does an Altered target site of an antibiotic protect a resistant bacteria against Antibiotics?
Can arise from acquisition of an alternative gene or a gene that encodes a target-modifying enzyme
You can acquire a gene which performs the same function but has a different structure and hence is not susceptible to the AB.
EXAMPLE: MRSA acquired a gene which produces an alternative penicillin binding protein - it performs the same function but has lower affinity to beta-lactams so methicillin is ineffective.
How does an Decreased drug accumalation of an antibiotic protect a resistant bacteria against Antibiotics?
Reduced penetration of AB into bacterial cell (permeability) and/or increased efflux of AB out of the cell – drug does not reach concentration required to be effective.
How do the genes spread?
Genes spread via Mobile elements? -Plasmids -Conjugation -Transduction -Transformation
What are the Sources of antibiotic resistance genes
Plasmids – extra-chromosomal circular DNA, often multiple copy. Often carry mutliple AB res genes – selection for one maintains resistance to all. Transposons. Integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome and vice versa. Naked DNA. DNA from dead bacteria released into environment.
Summarise the mechanism of action of some important antibiotics?
Selective toxicity- key differences between host and bacterium. Beta-Lactams, vancomycin-cell wall DNA Replication- Erythromycin, chloramphenicol and tetracycline-protein synthesis.
What is the mechanism of action for Beta-lactams?
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall. Examples include Penicillin and methicillin. Bind to penicillin-binding proteins. PBPs catalyse a number of steps in the synthesis of peptidoglycan. Beta-lactams bind PBPs with high affinity and inhibit their function (except PBP2a of MRSA!).
What is the mechanism of action for Tetracycline?
Inhibits protein synthesis. Binds to the 16S component of the 30S ribosomal subunit, preventing the interaction of charged aminoacyl-tRNAs with the mRNA/ribosome complex. This prevents the elongation of the peptide
What is the mechanism of action for Chloramphenicol?
Inhibits protein synthesis. Binds to 50S ribosomal subunit and blocks peptidyl transfer step. Often used topically due to toxicity. However, increasing AB resistance is renewing interest in Chloramphenicol as a systemic therapeutic.
What is the mechanism of action for quinolones ?
Interferes with DNA synthesis
Targets DNA gyrase (in Gram NEGATIVE) and Topoisomerase (in Gram POSITIVE)
DNA gyrase and topoisomerase is responsible for unravelling DNA
Name Other reasons for treatment failure
Inappropriate choice for organism
Poor penetration of AB into target site
Inappropriate dose (half life)
Inappropriate administration (oral vs IV)
Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase
How do you measure resistance?
Very important to consider that measurements made in vitro may not fully reflect the situation in vivo! Swabs are typically streaked out onto diagnostic agar to identify causative organism. Once identified, the pathogen streaked over a plate and then over-laid with AB-containing test strips or discs. Other approaches include broth micro-dilution and PCR detection of resistance genes.
Why do hositals provide a strong selective pressure for AB resistance?
Large numbers of infected people receiving high doses of antibiotics - strong selective pressure for emergence/maintenance of AB resistance
What are the risk factors for HAI (hospital acquired infection)
High number of ill people! (immunosuppression) Crowded wards Presence of pathogens Broken skin – surgical wound/IV catheter Indwelling devices - intubation AB therapy may suppress normal flora Transmission by staff – contact with multiple patients
What are antibiotic resistance associated with?
-Increase morbidity -Increase mortality -Length of hospital stay -Cost
What illnesses can Staphylococcus aureus (MRSA,VISA) cause?
MOSTLY SKIN INFECTIONS
S. aureus can cause a range of illnesses, from minor skin infections, such as pimples, impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, bacteremia, andsepsis.
What illness can Clostridium difficile cause?
Pseudomembranous colitis, antibiotic-associated diarrhoea
Pseudomembranous colitis refers to swelling or inflammation of the large intestine (colon) due to an overgrowth of Clostridium difficile (C difficile) bacteria. This infection is a common cause of diarrhea after antibiotic use.
What illness can E.coli (ESBL) cause?
GI Infect, Neonatal meningitis, UTI, Strepticaemia
What illnesses can Acinetobacter baumannii (MDRAB) cause?
Oppurtunistic
Pneumonia
Bloodstream Infections
Meningitis
Wound and surgical site infections, including flesh eating bacterium necrotizing fasciitis
Urinary Tract Infections
What illness can enterococcus (VRE) cause?
UTI, bacteraemia, infective endocarditis
What do sulphonomides do?
INTERFERES WITH FOLATE PATHWAY
Bacteriostatic
Used to treat UTI, Reproductive Tract Infection (RTI) and bacteraemia
What do Aminoglycosides do?
Affect PROTEIN SYNTHESIS
Affects RNA PROOFREADING which leads to misfolded proteins
Some of these proteins are incorporated into the membrane and allow leakage so the cells rupture.
Has toxicity issues
What do Macrolides do?
Interferes with protein synthesis
EXAMPLE: Erythromycin
Gram POSITIVE infections
Targets 50S ribosomal subunit preventing aminoacyl transfer
Causes truncation of polypeptides
truncation=to shorten by or as if by cutting off.
