Micro/ID Set 2

E. coli, Klebsiella pneumonia, Proteus mirabilis

MacConkey Agar, LF = pink; NLF = gray/white (not pink) lactose is for pussies

UTI, Gastroenteritis/colitis, meningitis, bacteremia, pneumonia, wounds and abscesses

Klebsiella pneumonia

Proteus mirabilis and Proteus vulgaris

EIEC, STEC, Campylobacter, Salmonella, Shigella

E. coli (ETEC, EAEC)

STEC (Shiga Toxin-producing E. Coli), Shigella

Eating bad meat or the poo of a bad-meat-eater, Contaminated food (beef, beef jerky, apple cider, lunch meat, milk, yogurt), Contaminated water, Person to person spread in daycares/wading pools

Shigella, Enterohemorrhagic E. Coli (EHEC)

Get poo, find shiga toxin, Recovery of organisms in stool (reliably detects only sterotype O157:H7 – most common serotype associated with disease), Detection of toxin in stool samples , Cell culture using Vera cells, Enzyme immunoassay (EIA) methods, PCR to detect toxin genes

US – Shigella sonnei (D); Worldwide – Shigella dysenteriae (A)

Antibiotics are used to prevent disease transmission (high infectivity rate -- <200 organisms needed to cause disease), Downsides are that run risk of bacteria developing antibiotic resistance – ampicillin resistance is common, so already have to treat a self-limiting disease with TMP/SXT, quinolones, third generation cephalospirins

Risk factors – improper food handling; age (children<5 YO, adults>70YO most commonly infected), Samlonella typhimurium and Salmonella enteriditis serotypes = major causes of disease

Salmonella typhi and Salmonella paratyphi

Salmonella typhimurium or Salmonella enteriditis – diarrhea, non typhoidal

1. Decreased absorption of fluid, Inhibited/defective absorption from villous cells, Luminal presence of osmotically active agents, Decreased contact time (rapid transit time), 2. Increased secretion of fluid, Stimulated anion secretion from crypt cells

Correction and prevention of dehydration due to GI fluid loss by increasing absorption of sodium and water from small intestine via glucose/NA symport – it does not stop diarrhea

Eating undercooked shellfish (since it grown well in sea-water and normally inhabits coastal waters), Mild diarrhea beginning 24 hours after consuming contaminated food; potentially accompanied by nausea, vomiting, low-grade fever., Usually self-limiting in 2-3 days

Ingestion of seafood or through wounds following exposure to salt water, Blood stream infection. Underlying severe liver disease predisposes patient to severe infection

Campylobacter jejuni, Campylobacter coli CLUCK CLUCK!

Demyelinating autoimmune, ascending paralysis, campylobacter, “An acute inflammatory demyelinating polyneuropathy (AIDP), an autoimmune disorder affecting the peripheral nervous system, usually triggered by an acute infectious process. It is frequently severe and usually exhibits as an ascending paralysis noted by weakness in the legs that spreads to the upper limbs and the face along with complete loss of deep tendon reflexes.” (from Wikipedia), Associated with O19 serotype of Campylobacter

Listeria, Clostridium difficile

1. Inhibit the cross linking of peptidoglycan strands catalyzed by a transpeptidase, They bind covalently with the enzyme forming an acylated enzyme that’s inactivated, Penicillin is a structural analogue of D-Ala-D-Ala, The beta lactam ring is in the same position as the peptide bond., 2. Autolysins play a role through continued dissolution of cell wall in absence of synthesis

Gram positive, (Strep), Anaerobes (Oral (“above the belt”).)

Bactericidal, PAE for Gram + only, Time dependent

Side effects – GI symptoms, sodium overload, bone marrow depression, hepatitis, platelet aggregation, seizures, hypersensitivity (acute allergic) reaction

Drugs that compete with penicillin for access to beta lactamase (which cleaves and inactivates penicillin) active site. Beta lactamase irreversibly hydrolyzes beta lactam ring of beta lactamase inhibitor rather than penicillin

Primarily only active against Class A serine hydrolases (except Tazobactam, which has substantial Class C and D reactivity), Degraded by Beta lactamase after binding, Clavanulate induces Beta lactamase expression, Inhibitor resistant Class A enzymes have emerged, One given organism produces multiple classes of Beta lactamases, Multiple organism infection produce different Beta latamases

Avoid anaphylactic shock from acute allergy, To identify whether or not a patient is allergic to penicillin in an attempt to avoid administering the drug to an individual who is ACUTELY ALLERGIC to it and would go into anaphylactic shock if given penicillin

Aminopenecillins increase spectrum of activity of penicillins +enterococc, dumb GNR, Like PCN, pneumococcus and streptococcus, but also enterococcus, and some gram negatives including H influenza, E coli, Proteus mirabilis, Salmonella

Adding beta lactamase increases spectrum to include beta lactamase producing strains of Staph aureus, H influenza, M catarrhalis, many GNRs

Piperacillin = GNR + more GNR + Pseudomonas

Methicillin (or similar penicillinase-resistant penicillin) oxicillin is PCNase resistant

Prevents cell wall synthesis by binding to enzymes called penicillin binding proteins (PBPs). These enzymes are essential for the synthesis of the bacterial cell wall., PAE versus Gram + organisms, Time dependent killing

Up to 33%

Ceftriaxone QD!

4th generation (i.e. cefeprime)

2nd Generation (i.e. cefoxitin)

Very broad, nosocomial infections, Gram positive – (Except Enterococcus faecium and MRSA), Gram negative including pseudomonas, Anaerobes including bacteroides, Note – Ertapenem – narrower GNR spectrium, community acquired infections, PAE for BOTH GRAM + AND GRAM –

NO

Yes

NO

YES

YES

YES

Aztreonam (no cross-allergenicity with penicillins)

C difficile colitis

NO

No. The is “red man” syndrome that results from rapid IV vancomycin dosing. She should only temporarily stop the infusion or slow it down, not cease completely.

Allergenicity (skin rash, eosinophilia, drug fever), Phlebitis, “Red man” – flushing with rapid IV dosing, Doubtful ototoxicity and nephrotoxicity

Calcium dependent cytoplasmic membrane binding, Oligomerizes disrupting membrane, Release of intracellular ions and rapid cell death, Uses – resistant gram positive infections, skin and soft tissue infections

Mechanism of Actions: Inhibition of protein synthesis, Bind to bacterial 30S ribosomal A site rRNA, Misreading of genetic code, “Freezes” the initiation complex and stops process, Active transport into bacteria with accumulation and retention, Illicit use of polyamine transported, Inhibited by chloramphenicol, calcium, anaerobic environment, acidic environment, genetic changes, Concentration dependent killing, PAE against Gram + AND Gram -

Synergy – Beta lactams, Antagonism -- chloramphenicol

Gram Positive

1. Nephrotoxicity: 10-20%, Proximal tubular changes in all, Glomerular changes in a few, Reversible; 2. Ototoxicity: Uncommon, Cochlear (3-14%) Can’t hear, Vestibular (4-6%) Lucille 2, Irreversible 3. Neuromuscular paralysis, VERY RARE

Take advantage of concentration dependent killing, PAE, fact that renal tubular/inner ear cell uptake saturated at low concentrations while minimizing total time of drug exposure to limit adaptive post-exposure resistance and side effects Also limit tox

Binds to smaller 30S A site rRNA, Inhibits shift from A/T to A/A

Spectrum of Activity All the weird ones: Chlamydial Infections, Borella budorferi, H. pylori (in conjunction with other Abs, bismuth subsalicylate), Borrelia recurrentis (relapsing fever), Brucellosis (with Gentamicin in very ill patients), Calymmatobacterium granulomatis (granuloma inguinale), Chelation with calcium, deposition with calcium in teeth/bones, Upon exposure to sunlight, darkened bands appear on teeth, Important from last few days of pregnancy through about 6 years

Binds to larger (50S ribosomal site rRNA) hits 50S, Inhibits peptide bond formation, catalyzed by peptidyl transferase , Binding site overlaps with Linezolid, Clindamycin, and Macrolide

Strep pneumonia (CIDAL), Neisseria meningitides (CIDAL), H influenza (CIDAL), Many gram negatives (STATIC), Many anaerobes (STATIC), Clinically, used to treat CNS infections caused by above

CAN CAUSE APLASTIC ANEMIA, Not dose, plasma, or time related, Irreversible (>50%), Even though incidence is 1:40000 cases, often fatal, Proven causal relationship on epidemiological grounds

Binds to larger (50s) ribosomal A and P sites 23S rRNA, Inhibits peptide bond formation catalyzed by peptidyl transferase, Binding site overlap with Linezolid, Chloramphenicol, and Macrolides

Gram positive cocci, S pneumonia, Group A strep, Staph aureus, Most anaerobes

Pseudomembranous Colitis C.diff colitis

Mechanism of Action: Binds to large 50S ribosomal P site rRNA, Inhitits formation of 70S initiation complex, Inhibits fMet-tRNA binding to P site, Inhibits EF-G mediated A to P translocation, Inhibit EF-P mediated peptidyl transfer, Overlaps Chloramphenicol and Clindamycin binding site, Spectrum of Coverage, “Worst of the worst” resistant from + organisms, Vancomycin resistant enterococcus 9VRE) E faecium, Methicillin resistant Staph aureus, PCN resistant Strep pneumoniae

Binds to larger (50S) ribosome rRNA near PTC, Blocks peptide exit tunnel, Allows 4-8 peptide bonds before peptide reaches tunnel, H-bonding via lactone ring and desosamine sugar, Overlaps binding site with Clindamycin and Chlorapmphenicol

Atypical organisms + GPC, Mycoplasma pneumonia, Chlamdia pneumonia, Legionella pneumophila, Penicillin Allergy, Strep pneumonia, Group A Strep

Non-fermenters = bacteria that DO NOT FERMENT CARBOHYDRATES, May oxidatively metabolize selective sugars, Common Organisms, Pseudomonas aeruginosa, Acinetobacter baumanii, Burkholderia cepacia complex, Burkholderia mallei and Buikholderia pseudomallei, Stenotrophomonas maltophilia

Pseudomonas and Burkholderia ox pos, Acinetobacter and Stenotrophomonas ox neg

EVERYWHERE, Soil, decaying organic matter, vegetation, water, Most relevantly, found throughout the hospital environment (moist reservoirs, food, cut flowers, sinks, toilets, floor mops, respiratory therapy, and dialysis equipment

YES

Bacteremia, Pneumonia, Chronic respiratory tract colonization and infections, Bone and joint infections, UTIs, Skin and soft tissue infections, including burn wounds, CNS infections, Eye and ear infections

Pseudomonas aeruginosa,

Antipseudomonal beta lactams, 4th generation cephalosporins, Carbapenms, Combos of any of the above with AG

Pseudomonas aeruginosa, Acinetobacter species

CF patients

Burkholderia pseudomallei

Gram negative diplococci

Epidemiology: Sexually transmitted disease, Humans are only host, 355,991 new cases reported in US in 2007, Incidence highest among sexually active young adults, Women and men can be asymptomatic and transmit infection, Clinical Characteristics, Women: Mucopurulent cervicitis, urethral syndrome, pelvic inflammatory disease, Neonates: Ophthalmia neonatorum, Gonococcal scalp abscesses, Systemic infections, Men: Urethritis, Epididymitis, Rectal infections

Neisseria gonorrhoeae, Gram stain of urethral sample, bacterial culture with selective media at 35-37C, 5% CO2 for 72 hours (organisms small, glistening, raised), nucleic acid amplification methods, Definitive ID requires demonstration of glucose utilization, hydrolysis of prolyl-hydroxyl aminopeptidase, immunologic methods (specific monoclonal Abs directed againstouter membrane proteins), Prevention – sex education, abstinence, use of condoms

Asymptomatic nasopharyngeal carriage ranging from 8-25%, Colonization increases in closed populations, , In USA, >98% of cases are sporadic, Case ratios about 1400-2800 per year (stable), Localized outbreaks due to serogroups C and Y have increased since 1991, Serogroups B, C, and Y are the major causes of disease, Case fatility rates ~ 10-14%, Infection occurs soon after colonization if it is going to happen, Groups B, C, Y are most severe, Recurrent and severe infections associated with deficiencies in C5-C9 in complement cascade

Bacteremia without sepsis, Meningitis – neurologic sequelae, Sudden onset of fever, chills, myalgias, arthralgias followed by signs of acute bacterial meningitis (headache, confusion, nuchal rigidity) flu sx then meningitis sx, Leukocyte count approximately 1200 cells/mL; low serum glucose, high serum protein (about 5X normal levels), Meningococcemia, Waterhouse-Frederishen Syndrome – adrenal insufficiency

Poorly immunogenic in children < 18 months, Does not confer long-lasting immunity, Does not cause a sustainable reduction in nasopharyngeal carriage

For general population:Patients 11-19 YOs – single dose MCV4 at 11-12 years or high school entry, For groups at increased risk, 2-10 YOs – Single dose MCV4, 11-19 YOs – single dose MCV4 (preferred), 20-55 YOs – single dose of MCV4, >55 YOs – single dose of MPSV

People with asplenia, complement deficiencies, Travelers to highly endemic areas, Closed populations, Clinical laboratory workers

Diagnosis – meningococcal meningitis (caused by Neisseria meningitides), Treatment – Penicillin (or ceftriaxone or chloramphenicol if allergic to penicillin), Prophylaxis – those in close contact with the patient – prescribe rifampin, ciprofloxacin, or ceftriaxone, Prophylaxis for all forms of meningitis – NO – use Gram stain (Gram -) to determine necessary prophylaxis, Don’t have to worry about Listeria (Gram +), for example