Micro bio exam 3

Beta lactam

Kill bacteria by binding to penicillin binding proteins (PBPs) and inhibiting cell wall synthesis

B lactamase enzymes break B lactam of ring of these antibiotics → make them ineffective

Beta lactam family: Natural

Examples: Penicillin G, Penicillin V

Spectrum: Narrow; mostly gram positive

Beta lactam family: Penicillinase resistant

Examples: Nafcillin, oxacillin, dicolxacillin

Spectrum: Anti - staphylococcal; oxacillin used for MRSA testing

Beta lactam family: Aminopenicillins

Examples: Amipicillin, amoxicillin

Spectrum: Broad spectrum, extends to some gram negative

Beta lactam family: Extended / antipseudomonal

Examples: Ticarcillin, piperacillin

Spectrum: Adds pseudomonas and other resistant gram negatives

Beta lactam family: Beta lactamase inhibitor

Examples: Amoxicillin - clavulanate, piperacillin - tazobactam, ampicillin - sulbactam

Spectrum: protect the antibiotics by binding to and inactivating these enzymes, allowing B lactam to remain active against bacteria

Glycopeptides

Bind to peptide precursors, preventing cell wall formation and weakening the bacterial cell wall

Example: vancomycin

“last resort to GPC MRSA”

Cephalosporins (5 generations)

BETA LACTAM

disrupting bacterial cell wall synthesis, leading to cell lysis and death. generally have a broader spectrum of activity and higher resistance to certain beta-lactamase enzymes

Examples:

1st gen: Cefazolin

2nd gen: Cefuroxime, cefoxitin

3rd gen: ceftriaxone, ceftazidime

4th gen: cefepime

5th gen: Ceftaroline

Cephalosporins (5 generations)

WHAT TO REMEMBER

Gram postive & Gram negative coverage rises across generations

Antipseudomonal: ceftazidime (3rd) & cefepime (4th)

Covers MRSA: Ceftaroline (5th)

Carbapenems

BETA LACTAM

“big guns”

Examples: Meropenem, ertapenem, imipenem (doripenem)

Broad spectrum: GP, GN, ESBL producers, anaerobes, (NOT MRSA). Ertapenem does NOT cover: Pseudomonas, enterococcus, or aacinetobacter

Mono bactam

BETA LACTAM

Examples: Aztreonam - the only clinically relevant one

spectrum: GRAM NEGATIVE ONLY!!!!

*******USUABLE IN PATIENTS WITH PENICILLIN OE CEPALOSPORIN ALLERGY*********

Resistance to remember (Beta lactams + Glycopeptides)

Gram negatives are resistant to vancomycin (too large for the outer membrane

Gram positives are resistant to aztreonam

B lactamase enzymes: break B lactam ring of these antibiotics → ineffective

Aminoglycosides

Protein synthesis inhibitor: irreversibly binds to 30s ribosome → interferes with initiation complex

mRNA misreading → abnormal/nonfunctional proteins

Bactericidal

Uptake: O₂ Dependent active transport → ineffective against anaerobes or in acidic environments

Neurotoxicity, Allergic reactions, Nephrotoxicity, Ototoxicity

Aminoglycosides examples

Tobramycin

Amikacin

Neomycin

Gentamicin

Streptomycin

Tetracyclines

Bind reversibly to the 30s ribosomal subunit ;

Block attachment of aminoacyl - tRNA to the A site

Bacteriostatic effect (inhibit growth, not directly kill)

Broad spectrum: against many Gram positive and Gram negative bacteria

-Rickettsia

-Chlamydia

-Mycoplasma

Tetracycline toxicity

CNS

Hepatotoxicity

Renal toxicity

Teeth and bones

Gastrointestinal and microbiome effects

Photosensitivity

Tetracyclines exampels

Tetracycline

Doxycycline

Minocycline

Tigecycline (a glycylcycline derivative)

Macrolides

Binds to the 50s ribosomal subunit (23 rRNA)

Blocks translocation step - movement of the peptidyl tRNA from the A site to the P site during elongation

Bacteriostatic (can be bactericidal @ high concentrations)

spectrum: Respiratory infections and STIs

Macrolides examples

Erythromycin

Azithromycin

Clarithromycin

Lincosamides

Binds to the 50s ribosomal subunit (23 rRNA)

Blocks translocation step - movement of the peptidyl tRNA from the A site to the P site during elongation

Bacteriostatic (can be bactericidal @ high concentrations)

spectrum: Respiratory infections and STIs

Anaerobic; inducible resistance is why D zone exists

Lincosamides examples

Clindamycin

Lincomycin

Macroslides and lincosamides resistance

Efflux pumps (mef gene in streptococcus pneumoniae)

Methylation of 23s rRNA (erm genes → res phenotype)

Chloramphenicol

Acts on bacterial ribosome, specifically binding to the 50s ribosomal subunit

inhibits the enzyme peptidyl transferase (forms peptide bonds between amino acids during protein synthesis)

Bacteriostatic

Bactericidal against: Haemophilus influenzae, Neisseria meningitis, bacteroides sp, brucellosis, and UTI

Broad spectrum: anaerobic & aerobic bacteria

Chloramphenicol :(

Crosses Blood brain barrier, causes aplastic anemia

Oxazolidinones: Linezolid

Binds 50s subunit (23s rRna)

Blocks 70s initiation complex formation - prevents translation from starting

Bacteriostatic

Spectrum: Last resort for gram positive: MRSA, VRE, Penicillin resistant streptococcus pneumoniae

Oxazolidinones: Linezolid resistance

Efflux pumps remove the drug from bacterial cells

Ribosomal protection proteins (optra, poxtA) block drug binding

Fluoroquinolones

Nucleic acid synthesis (DNA)

Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV enzymes essential for supercoiling

(prevent DNA replication and transcription → bacteria death

Bactericidal

Spectrum: Anaerobes and certain Protozoa (Trichomonas, giarda, entamoeba)

Fluoroquinolones and resistance

Cipro, levo, moxiflocacin

BAD:

Tendon rupture, neuropathy, CNS and behavioral effects

Rifamycins (rifampin)

Bind to the beta subunit of bacterial DNA - dependent RNA polymerase

(inhibit initiation of RNA transcription, blocking mRNA synthesis

Bactericidal

Spectrum: gram positive mycobacterium tuberculosis (essential drug in tuberculosis therapy), leprosy, and meningitis prophylaxis

***rapid resistance so never used alone***

Rifamycins (rifampin) resistance

Mutations in rpoB gene alter RNA polymerase binding site

Develops rapidly if used alone → combination therapy

BAD: causes orange red discoloration of body fluids (urine, tears, salivia)

Metronidazole

Reduced to free radicals → DNA strand breaks

Bactericidal

Spectrum: effective against anaerobes and protozoa

-Gardnerella vaginalis

-Trichomoniasis

-Giardiasis & amebiasis

-Clostridioides difficile colitis

-part of triple therapy for H. pylori

Metronidazole other [fix]

Bad:

Metallic taste, nausea, GI upset, reaction with alcohol (avoid during and 48 hrs after)

may cause dark urine or neuropathy with prolonged use

Sulfonamides

TARGETS FOLATE SYNTHESIS

competitive inhibition of para aminobenzoic acid (PABA), a substrate required for folic acid synthesis in bacteria

Examples: Sulfamethoxazole, Sulfisoxazole, sulfadiazine, urosulfans

Bacteriostatic

Spectrum: Typically used for UTI and STI

Trimethoprim

TARGETS FOLATE SYNTHESIS

Inhibits dihydrofolate reductase,

(the enzyme that converts dihydrofolic acid to tetrahydrofolic acid, the active form required for DNA synthesis)

Bacteriostatic [synergistic with sulfonamides]

Broad spectrum: UTI, GN sepsis, shigellosis, salmonella, pneumonia

Usually combined with Sulfamethoxazole / trimethoprim (bactrim)

Cotrimoxazole (trimethoprim sulfamethoxazole) TMP - SMX

Sequential blockade of folic acid synthesis - sulfonamide acts first, trimethoprim acts second

Bactericidal

Spectrum: UTI, pneumocytis jirovecii pneumonia, nocardia infections, and some MRSA skin infections

Combined drug (synergistic)

Nitrofurans

Multi target: DNA, ribosomal proteins, metabolic enzymes

Bactericidal

Spectrum:

GP: Staph saprophyticus, Enterococcus faecalis, some Staph auerus

GN: E.coli, enterobacter spp, klebsiella spp, citrobacter spp

For uncomplicated lower UTIs, Prophylaxis for recurrent cystitis, not used for pyelone or systemic infections (low serum lvls)

Nitrofurans otro [fix]

Examples:

Nitrofurantoin (Macrobid, marcodantin)

Not used in pseudomonas, proteus, serratia, acinetobacter

Vibro found in + infection

Aquatic environment (fresh, brackish, salt water)

Oysters

contract by drinking contaminated water or food

⬆outbreaks with social upheaval and poverty, natural disasters, war

(untreated → 50% mortality from dehydration)

Endemic area have some immunity

Characteristics of vibro

Gram negative comma (curved) rods

-Motile by polar flagellum

💜🎈oxidase positive + indole positive

🐮NLF on macconkey plate

(slightly pink so be careful)

🧫Best agar for growing is TCBS: Orange colonies

Thiosulfate citrate bile salts agar plate

Vitek + MALDI

Vibro sp

V. cholerae non O1

Causes epidemics + Toxin producers

V. cholerae serogroup 01

V. cholerae serogroup O139 (newest 1992)

Wound infection

Vibrio vulnificus

Vibrio haemolyticus

Oysters
V. parahemolytics

Vibro mimicus

Vibro alginolyticus: least pathogenic for humans (hazard for fishermen or sailors)

Vibro cholerae non 01

Lacks toxin gene

Milder infection

Infects ear, gallbladder

May cause cellulitis

Serves as natural vaccine against more virulent strains

-Areas with cholera endemic are more likely to get vaccinated vs places with low infections

Vibro cholerae 01

Causative agent of cholera

Big endemic in 3rd world countries

Vibro cholerae

Reasons for increased # cases

-consumption seafood (raw / undercooked)

-immunocompromised hosts

-breakdown of public health and sanitation

Vibro parahemolyticus

Enteritis (summer diarrhea in Japan)

Most coastal states in US, Canada, and Europe

Hemolysin production: Virulence

-heat stable

Consumption raw, undercooked seafood (oysters)

Wounds

Vibro vulnificus

Wounds: bulla (big blisters)

-Traumatic injury (sea water or brackish water)

-cellulitis

Primary septicemia: after ingestion raw shellfish (oysters)

-40 - 60% mortality

Pathophysiology of vibro

Cholera toxin: primary virulence factor, organism does not penetrate intestinal mucosa

Receptor on cells of small intestine

Activates adenylate cyclase enzyme:

⬆cAMP in cells

Secretion of water, Na, K, Cl, HCO3, to lumen

Vibrio treatment

Wounds, blood

Doxycycline

Ciprofloxacin

Levofloxacin

Moxifloxacin

SXT

D.C.L.M

Cholera is not treated with antibiotics rather they are treated with electrolytes

Cholera treatment

ORS or IV fluids

Oral electrolyte and fluid (if very ill then IV)

Rehydration → mortality reduce to <1%

TCBS

Thiosulfate citrate bile salts agar plate

Selective

Thiosulfate, citrate, bile salts, sucrose

sucrose fermentation

(+) V. cholerae, V. alginolyticus, and V. vulnificus

(=) V. parahemolyticus & V. vulnificus

V. Vulnificus is lactose (+)

Cholera symptoms

Toxin (enterotoxin) induced

Vomiting

Fever rare

Cramps

“rice water stool” (watery diarrhea)

Rapidly fatal

-Electrolyte imbalance → dehydration

-hypotensive due to dehydration

Lab ID of vibro

Specimen: stool, tissue, wound aspirates, or swabs

BA: medium to large colonies ; small opaque

Iridescent w/ greenish hue

alpha or beta hemolysis

Aeromonas characteristics

💜🎈oxidase positive + indole positive

Glucose fermenter

Gram negative rod (straight!)

virulence factors: endotoxin, hemolysin, proteases

Aeromonas found in

Fresh, brackish, salt water

isolated from animals/ meat

Aeromonas hydrophila

Multiple intestinal presentation

-acute secretory diarrhea with vomiting

-acute dysentery w/ blood & mucus in stool (similar to shigellosis)

-chronic diarrhea usually lasting more than 10 days

-Cholera like with rice stool

Traveler’s diarrhea (similar to enterotoxigenic E. coli)

TREATMENT IN IMMUNOCOMPROMISED PATIENTS!!!

A hydrophila complications :(

Hemolytic uremic syndrome

Kidney disease

A caviae

Species most frequently associated with GI infections

A hydrophila sick :(

Extra-intestinal

- Septicemia

-Rare progress to meningitis, endocarditis

Wounds

Traumatic

🩸transmitted by leeches

Aeromonas ID

Grows on

BA: large, round raised, opaque,

strong odor (like 🤮), translucent: white or buff, some are 🅱 hemolytic

MAC (NLF)

If wound or stool: Automated ID panels work, and MALDI

Aeromonas treatment [?]

3rd gen cephalosporins such as ceftriaxone, fluoroquinolones, or SXT

A. veronii- sus to cephalothin + cefoxitin

Aeromonds resis

Penicillin, ampicillin, and carbenicillin

Campylobacter characteristics

Curved GNR (seagull or “s” “c”)

-faint so use Carbol fuchsin as counterstain ⬆ stain time

💜🫧 Oxidase and catalase

➖ Urease negative

Fastidious (needs CO2)

Motility: darting (TSB)

Agar: runny looking / mucoid, gray to pink or yellow gray

Campylobacter reservoirs + agar

Reservoirs: chickens, wild birds, pigs, dogs, cats, sheep, and cows

(survives on chicken)

MAC, HE, and CAMPY set up for routine stool culture

Campylobacter jejuni

How is it aquired?

Most common cause of bacterial gastroenteritis worldwide

Direct contact: infected animals (🐱, 🐶, 🦜) & person to person

Indirect: consumption of water, dairy products, and poultry

Campylobacter jejuni

infections

Diarrheal disease: 2 - 10 days after ingestion

mild abdominal pain → cramps + bloody dirrhea, fever & chills

Guillain - Barre syndrome: autoimmune disorder → paralysis

Campylobacter jejuni

Collection and culturing

Stool → use cary blair transport media

Selective:

• Campy BAP

• Brucella agar

• Charcoal selective media

• Campy bag (⬆CO2 ⬇O2)

• Mircroaerophilic

C jejuni

characteristics

Hippurate and indoxyl acetate ➕

sus to nalidixic acid

BA: C.jejuni is moist and runny looking, non hemolytic

Direct stool test

Premier campy: detects antigens found on c. jejuni and C. coli in stool sample

Campylobacter treatment

No antibiotics unless severe infection

-Erythromycin

-Doxycycline

-Cipro (quinolone res is ⬆)