Gram Positive Bacteria Flashcards
Gram positive vs gram negative bacteria
Components of the cell wall of these two types of bacteria are the same (peptidoglycan).
Gram positive bacteria have a thick cell wall.
Gram positive bacteria cell wall picks up an iodine stain and stains purple.
Gram negative bacteria have an outer membrane in addition to a cell wall; this outer membrane causes problems with antibiotic resistance; between the cell wall and the outer membrane, there are efflux pumps, a space where resistance mechanisms can reside in the inner membrane space that can degrade antibiotics; this makes gram negative bacteria trickier to treat.
In gram negative bacteria, there are much more layers to get to the cell wall.
Because of the outer membrane, alcohol wash does not stay in gram negative bacteria and they pick up safarin to look red.
Some bacteria form in clusters, diplococci, elongated chain.
In general, gram negative bacteria tend to be smaller organisms.
Where do organisms reside in the human body?
The majority of the gram positives reside as colonizers on the skin, especially aerobic bacteria and on the mucous membranes. Gram negative bacteria reside in the urinary tract. Skin Large Intestine Stomach Nasopharynx Perineum Urogential Small Intestine Oral cavity
Gram positive bacteria
Staphylococci spp Streptococci spp Enterococcus spp Clostridium spp Corynebacterium spp Bacillus spp Lactobacillus spp Listeria spp Nocardia spp Propionibacterium Mycoplasma; does not stain well; GP in nature but an atypical because it doesnt stain, does not really have a cell wall; morphology is similar to that of a gram positive. Streptomyces All of the bacteria not ending with "cocci" are rods.
Microbial Resistance Evolution Harmless to Dangerous
The good (WT) The bad (multi-drug resistant) The really bad (extremely drug resistant); resistant to 3 or more classes. The CDC has 3 threat levels: Urgent Serious Concerning Most GP bacteria are serious, one that is urgent.
Staphylococci
Gram positive cocci in clusters
Species: aureus, epidermidis, capitis, lugdenensis, saprophyticus, hominis…
S. aureus: coagulase +
Colonize- skin, nose, axilla, groin.; normal colonizers.
Benign –> pathogenic
The coagulase test is a way to differentiate between S aureus and other staph; the organisms coagulate when you put coagulase on them indicates a positive result.
Staph aureus is the only coagulase positive, all other staph are coagulase negative.
Some patients have Staph aureus on them, some do not; if you do, you are more likely to be infected with it, but it is likely not going to be a severe infection.
Mostly benign, but if it gets into the wrong situation it can become a pathogen.
Staph aureus is a primary pathogen, meaning it causes infection in patients with no risk factors and patients with risk factors.
Staphylococus aureus
Primary human pathogen
Numerous infections:
-Skin and soft tissue
-Sinusitis
-Pneumonia
-Osteomyelitis
-Endocarditis
-Bloodstream Infections
-Meningitis
Multi drug resistance
High morbidity and mortality.
More likely to cause skin infections because it is sitting there on the skin.
The number 1 cause of bloodstream infections in the US, not in the world.
They colonize areas; attached to damaged valves and bones, joints; protein factors that allow it to attach to surfaces.
CDC classifies this as SERIOUS.
A lot of new drugs common to market that target S aureus.
MRSA
Has a lot of resistance and deaths with this organism.
Staph bacteria are a leading cause of healthcare-associated infections.
Resistance to methicillin and related antibiotics (nafcillin, oxacillin) and resistance to cephalosporins are of concern.
S. aureus has a ton of toxins sitting on the wall and inside the cell; TSS toxin produced in this organism and in Strep; virulent toxin.
There are other toxins that can cause rapidly fatal disease:
-TSST-1
-Enterotoxins
-Panton Valentine Leukocidin (PVL)
-Superantigen toxins
-Alpha-cytotoxins.
-Accessory gene regulator
-Microcapsule; ghost capsule; can have a capsule and survive without, so difficult to produce a vaccine against S. aureus.
-Slime-adhesion (biofilm) production; biofilm related infections; persistent; treat and cannot clear organism, tolerant, appears to be susceptible; slow down replication and can evade host defense pressures, quarm sensing state; difficult to kill and boil plays a large role in this.
-Tolerant to AB therapy.
Staphylococcus Epidermitis
Most common of the coagulase negative staph.
Can cause infection if you have access through which the patient can become infected (IV line, wound).
Not pathogenic, does not cause infection in normal healthy people.
-Often this is seen as a contaminant if you see it in culture.
-Adheres to prosthetic surfaces (biofilm formation) for infection:
Prosthetic joints, valves
IV, catheters
Other hardware.
Surgical site infections
Native bone.
Will not use repaid infection, it is not a pathogen, it is a colonizer.
Readily forms biofilms in patients, leads AB resistance that is tough to treat.
Slow progression of disease; AB targets are very low, a lot of resistance mechanism because it is a colonizer; biofilm production that causes resistance; bombarded with AB in skin and subQ layers and has built up resistance over time.
Staph aureus model of antibiotic resistance
Resistant staph in 1940 to penicillin because of penicillinases; 99% of staph have this.
Inherent mechanisms in place to be resistant to penicillin; produces penicillinase to degrade the penicillin.
Methicillin; semi synthetic penicillin; stable against penicillinases; used to be susceptible to methicillin; resistance in 1962.
Toxic
Methicillin resistance; encode resistance to almost every beta lactam available.
-Produces auxiliary penicillin binding protein; this is able to produce a cell wall when all other penicillin binding proteins are inhibited.
-Evade antibiotic and resist pretty much every beta lactam.
-MRSA encodes resistance to the backbone of antibiotic therapy (beta lactam antibiotics).
-Produce a 5th penicillin binding protein.
-Ceftaroline is a beta lactam antibiotic that does treat MRSA.
-Vancomycin took a long time to develop resistance, it is still low and a good drug, but problems are starting to emerge.
THEME: early introduction of antibiotics followed by resistance very readily.
Typically, MRSA is hospital acquired, but there are patients in the community that have MRSA.
Vancomycin Resistant S. aureus
Classically, vancomycin is not resistant, but it acquired a vancomycin resistant gene from plasmid from enterococcus.
Select strains are fully Vancomycin resistant.
13-15 islets identified throughout the world; 9 in Detroit-will this spread or is it just a single phenomenon.
CDC ranks this as concerning.
S. aureus epidemiology
Hospital associated:
-Multi drug resistant (MRSA); resistant to beta lactams, clindamycin, erthyromycin, tetracyclines: multi drug resistant.-Variety of infection types.
-Invades population at risk
-Reduced fitness; doesn’t cause rapid disease, slowly kills over time; submitted all cell working to resistance, not enough there for fitness and replication (not like Strep which is extremely fit).
-Less common virulence factors.
Community associated:
-Susceptible to many non beta lactams.
-Variety of infection types, but most commonly in skin infections.
-Invades normally healthy people
-Increased fitness; still has the MR gene, but it is a different gene and much smaller, which allows for more fitness; not harboring huge resistance on the genome; it has a ton of toxins still (TSST and enterotoxins).
Still MRSA, but there are more options to treat.
Not as drug resistant.
-More common virulence factors.
Streptococcus
Gram positive
Forms in elongated chains
Beta-hemolytic strep:
Group A: S pyogenes (strep throat)
Group B: S. agalactiae
Group C: S. eqius
Alpha-hemolytic strep:
S. pneumoniae
Viridans Strep: S mitis, anginosus, mutans, salivarius, gallolyticus (group D); in lab tests we do not often speciate Viridans strep because it does not matter, all have the same susceptivity and you treat with beta lactams.
Be concerned about Group A and Group B strep because of their pathogenicity.
Features:
-Lancefield classification based on CHO in cell wall off hemolytic strains: A, B, C, D, G, H, K; how do they lyse RBC is how they classify the organisms into different classifications.
-Produce a ton of toxins, super virulent pathogens; Toxin production: Scarlet fever, “flesh eating” bacteria.
-Often found in normal flora; in upper respiratory tract and not invading tissue.
-Infection types: cellulitis, abscesses, URI (upper respiratory tract infections like sinusoids and pharyngitis), LRI (lower respiratory tract infections like bronchitis and pneumonia), bacteremia, endocarditis, septic arthritis, neonatal sepsis (group B strep number one cause, delivered to baby as passes through birth canal that can lead to septic complications in the newborn).
Streptococcus Pneumoniae
Alpha hemolytic strep.
Pneumococcus
-Virulent and pathogenic diplococci; very virulent, causing infection in patients who have no risk factors for infection.
-Major cause of meningitis, otitis (ear infections), CAP (community acquired pneumonia), other URI; but it also is a colonizer of mouth nasopharynx (oral respiratory tract, so it is doing a normal function).
-Encapsulated (polysaccharide capsule)- over 90 serotypes, 23 of them cause major infections in humans.
Target for vaccine:
23 valent vaccine in adults
7 valent vaccine in children
13 valent in children (available since 2010); had to add valence for children and immunocompromised hosts; use this 13 valent vaccine also as a booster in adults over the age of 55 and in immunocompromised people.
-Reduced susceptibility to penicillins; mostly susceptible to macrolides, and flurouquinolones are becoming a concern.
-Organisms causing infection in adults and children are different.
Drug resistant Strep pneumo:
CDC ranks as Serious level
Excess hospitalizations and costs.
Leading cause of bacterial pneumonia and meningitis in the US.
Also a major cause of bloodstream, ear, and sinus infections.
Developed resistance to drugs in the penicillin and erythromycin groups (amoxicillin, Z-pak)
Macrolides and beta lactams are resistance mechanisms; emerging problem.
Strep. Pyogenes
Group A, beta hemolytic strep.
Common cause of strep throat, impetigo, scarlet fever, rhuematic fever, cellulitis (Staph aureus also causes cellulitis), necrotizing fasciitis (requires surgery to get rid of, the infection source, antibiotics do not cure this infection, they only slow down the rate of infection-group A strep is the leading cause of this infection), toxic shock syndrome.
Most common in children and the elderly.
Still highly sensitive to penicillin; it is the best agent against Group A strep, or beta lactams can treat; these are almost universally preferred; large amounts of these drugs are still safe, which is nice from a dosing standpoint.
There is hardly any beta lactam resistance with Group A strep; most common allergy in patients are beta lactams; if there is an allergy, you could treat wit ha macrolide, which is far inferior to beta lactams.
Group A strep is devloping resistance to macrolides like erythromycin; this is not due to direct treatment, jsut overuse of macrolides in general and strep come into contact with it.
Commonly used in things like respiratory tract infections; there is overuse and collateral damages leading to resistance.
Erythromycin Resistant Group A Strep: CDC rates as concerning.
Also resistance in clindamycin; erythormycin, azithromycin, clarithromycin.
Also has developed resistance to less commonly used drugs like tetracycline.
Strep throat hurts so bad because it is in a sensitive area and this organism produces a lot of toxins, there is a lot of inflammation.
Enterotoxins and exotoxins.
Strep. agalactiae
Group B, beta hemolytic strep.
Normal vaginal flora in up to 40% of women; if positive treat continuously during delivery.
Infection types:
-Children, #1 cause in neonatal sepsis.
-Immunocompromised adults: pneumonia, bacteremia, endocarditis, UTI, SSI, meningitis.
Penicillin treatment is still the most effective; universally susceptible.
Macrolides, streptogamin, lalcrlide: similar mechanism of action and collateral resistance.
It can be transmitted through the birth canal to babies and cause neonatal sepsis.
Endocarditis: bacterial infection of the heart leading to inflammation.
Clindamycin resitant Group B streptococcus; CDC rates it as concerning.
Also resistant to erythromycin and azithromycin.
Recently the very first cases of resistance against vancomycin reported in adults.
Strains with decreasing responsiveness to penicillins have been described, but still very rare.
Enterococcus
Gram positive cocci in chains.
Used to be streptococcus, it has similar staining and a chain like pattern.
Difference between enterococcus and strep: enterococcus is a gut colonizer.; big organism.
Metabolism is much different then strep; it is a functional anaerobc organism in the gut; it also has antibiotic resistance that is much different.
Can live in non oxygenated environment like our gut.
Normal flora in many anaerobic and aerobic environments.
Normal flora of the GI, mouth, female genital tract.
Not very pathogenic compared to Group A, but highly drug resistant.
Does not cause a lot of rapidly fatal disease.
Effects immunocompromised hosts or they cannot control the source.
Promiscuous organism; it likes to share things back and forth like plasmids and other genetic materials; other organisms can acquire resistant from enterococcus.
Significant resistance to many agents; gut organisms see a lot of antibiotics over lifetime.
Superinfection
Associated infections include bacteremia, IE, UTI, wounds, surgical site infections.
Organisms:
-E. faecalis: common, more antibiotic susceptible
-E. faecium: nosocomial, antibiotic resistant (aminoglycosides, beta-lactams, glycopeptides).
Vancomycin resistent Enterococci (VRE) continues to increase; this is the second line agent that we would use; fully resistant, genetic change that leads to this resistance; CDC ranks as a serious threat.
Macrolide resistance, fluoroquinolone resistance.
Very limited treatment options.
Infection vs Colonization; it is hard to tell if the enterococcus in your sample is pathogenic or just a colonizer.
