Antibacterials Pt. 1

Question 1

Selection of Appropriate Antibacterial Drug(s) (4):

Answer 1

1. Selective Toxicity
   
   • ​​risk vs. benefit
2. Type of organism
   
   • identification and susceptibility
   • empirical treatment: initial drug often chosen before culture results are known
3. Anatomical location of organism within human host
4. Host Status
   
   • age, allergies, renal/hepatic function, pregnancy, host defenses

Question 2

Definitions:

1. Bactericidal vs. Bacteriostatic
2. MIC vs. MBC

Answer 2

1. bactericidal (kills the bacteria) vs. bacteriostatic (stops the active growth of the bacteria but they remain viable)
   
   • host defenses are also important
2. MIC (Minimal Inhibitory Concentration) vs. MBC (Minimal Bactericidal Concentration — kills 99.9%+ of bacteria)

Question 3

time-dependent killing:

Answer 3

% of total time above MIC

• best clinical effect when remain 4-fold
  above the MIC for >50% of total time
• β-lactams

Question 4

Concentration-dependent killing:

Answer 4

Maximize the peak concentration (C_max)

• C_max/MIC ratio ≥8 is best
• Aminoglycosides
  
  • ​Have persistent effect even when levels fall below MIC

Question 5

Killing dependent on concentration x time:

Answer 5

Area under the curve

• AUC_24hr/MIC expressed in hrs
• Quinolones (also Cmax)

Question 6

Describe the Classes of Resistance Mechanisms (4):

Answer 6

1. Intrinsic Resistance
   
   • ​​fundamental properties of a given microbe
     
     • e.g. cell wall structure
2. Non-inherited Resistance
   
   • ​​cells not actively replicating
3. Mutations
   
   • ​​mutations that alter cells’ susceptibility to antimicrobial agent
4. Plasmid-mediated Resistance
   
   • extrachromosomal genes that encode resistance mechanism
     
     • potentially transferred to other microbes
     • multiple-resistance

Question 7

List the Antibacterials that Target the Cell Wall (8):

Answer 7

• ß-lactams
  
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams
  • ß-lactamase inhibitors
• Vancomycin
• Fosfomycin
• Bacitracin

Question 8

β-Lactams:

General Properties

Answer 8

• Bactericidal
  
  • bacteriostatic under some conditions
• Effective against gram-pos. and -negative bacteria
• Activity is maximal on actively growing bacteria

Question 9

β-Lactams:

Mechanism

Answer 9

• Inhibit transpeptidases (penicillin-binding proteins or PBPs) which catalyze cell wall crosslinks
  
  • β-lactam covalently binds to PBPs
  • competitive, irreversible
• β-lactam ring is a 3-d analog of D-Ala-D-Ala linkage in peptidoglycan side chain
• Bacterial lytic enzymes enhance breakdown of
  crosslinks, accelerate cell lysis
  
  • Rapid bacterial lysis can cause symptoms due to release of bacterial components
  • chills, fever, aching

Question 10

Resistance to ß-lactams:

Answer 10

1. β-lactamase:
   
   • ​​most prevelant
   • cleaves β-lactam ring
   • extracellular activity:
     
     • β-lactamase can protect other bacteria in the vicinity
2. Altered PBP(s):
   
   • will not bind β-lactam effectively
   • methicillin-resistant Staph.; penicillin-resistant
     Strep. pneumoniae
3. β-lactam agent cannot reach PBPs:
   
   • intrinsic resistance of some gram-negatives

Question 11

β-Lactams are ____ _________ killers:

Answer 11

time-dependent

• Keep the drug 4-fold above the MIC for >50% of total treatment time
• Since β-lactams have short t_1/2 ⇒ shorter dosing intervals

Question 12

Penicillins:

Common Properties

Answer 12

• well distributed to most areas of the body
  
  • low penetration into CSF, but this increases during meningitis
• some may be given orally, otherwise via IV or IM
• short half-lives
  
  • 30 min to a few hours
• renal elimination - anion transport

Question 13

List of Penicillins (7):

Answer 13

1. **penicillin G **
2. penicillin V
3. oxacillin
4. amoxicillin
5. ampicillin
6. ticarcillin
7. piperacillin

Question 14

penicillin G & V:

1. Route:
2. Spectrum:

Answer 14

1. **Route: **Oral (pen V) vs. IV/IM (pen G)
2. **Spectrum: **(V is more acid stable than G)
   
   • for gram-pos. and gram-neg. cocci
     
     • non ß-lactamase producing
   • gram-pos. anaerobes
     
     • Clostridium, Peptococcus, Peptostreptococcus, Veillonella, Actinomyces
     • not Bacteriodes fragilis
   • Streptococcus pneumoniae (20-30% resistance)
   • most other Strep.
   • Neisseria meningitidis meningitis
   • Syphillis
   • good activity against:
     
     • anthrax (Bacillus anthracis)
     • Listeria, Actinomyces

• **Tidbit: **t_1/2 can be extended if combined with procaine or benzathine
  
  • IM pencillin G + benzathine for syphillis

Question 15

What antibacterial drug would you use to treat ß-lactamase producing Staphylococci?

Answer 15

Oxacillin

• “methicillin”-type drug
• given IM or IV
• reasonable activity against most streptococci
• Staph. aureus that are sensitive to these drugs are
  called MSSA (methicillin-sensitive Staph. aureus)

Question 16

Ampicillin, Amoxicillin:

Spectrum

Answer 16

• various β-lactamase-negative gram-pos:
  
  • Listeria, Streptococcus, etc.
  • Enterococcus (e.g. urinary tract infections)
• gram-neg:
  
  • including Haemophilus, Neisseria, Escherichia, Salmonella
• High dose amoxicillin is the drug of choice for **otitis media **in otherwise healthy children
• Amoxicillin alternate choice for Lyme disease

Question 17

Ampicillin vs. Amoxicillin:

Answer 17

• Amoxicillin: better absorbed after oral dose
• Ampicillin: available IV or oral
• Ampicillin has 2 important uses that amoxicillin doesn’t:
  
  1. Meningitis (e.g. Neisseria, Listeria):
     
     • ampicillin available IV
     • amoxicillin only orally
  2. GI infections:
     
     • esp. Shigella
     • Less absorption of oral doses = more in GI tract

Question 18

Penicillins with extended gram-negative spectrum (2):

Answer 18

1. ticarcillin
2. piperacillin

Question 19

Ticarcillin:

Answer 19

• broad gram-neg, effectiveness extended to include:
  
  • Pseudomonas aeruginosa
  • some Enterobacter and Proteus, E. coli
  • susceptible to β-lactamases
  • sometimes used with aminoglycoside
• some anaerobes
  
  • when combined with β-lactamase inhibitor
  • ticarcillin + clavulanate
• Retain some gram-pos. activity
• given IM

Question 20

Piperacillin:

Answer 20

• broad gram-neg. spectrum including:
  
  • some Pseudomonas and Klebsiella
  • including those that are ticarcillin resistant

Question 21

Excretion/metabolism of penicillins:

Answer 21

• mostly renal
  
  • 20% glomerular filtration
  • 80% tubular anionic excretion
• ≈ 30% hepatic metabolism

Question 22

Adverse reactions of penicillins (7):

Answer 22

1. Allergic rxns can be VERY SEVERE, incl.:
   
   • ​​anaphylaxis (low incidence but VERY important)
   • serum sickness, delayed hypersensitivity
   • rash <8%
   • Use of Pre-Pen can help with predicting an allergic rxn
2. fever (4-8%)
3. diarrhea (< 25%)
4. enterocolitis (~1%)
   
   • NOTE: all antibacterials can cause enterocolitis!
5. elevated liver enzymes (1-4%)
   
   • hepatotoxicity
6. hemolytic anemia (low incidence)
7. seizures

Question 23

Administration of penicillins:

Answer 23

• some IV or IM only
  
  • penicillin G, azlocillin, ticarcillin
• some oral
  
  • ampicillin, amoxicillin, penicillin V, dicloxacillin
• generally well-distributed to most areas of the body
• generally short half-lives
  
  • ​procaine and benzathine penicillin are slow-release IM forms ⇒ substantially increase the duration of action
• inflamed meninges ⇒ increased CNS distribution

Question 24

β-Lactamase inhibitors:

Answer 24

• clavulanic acid, tazobactam, sulbactam:
  
  • β-lactam analogs that bind irreversibly to β-lactamase
• limit hydrolytic cleavage of β-lactams by some types of β-lactamases (Class A; some Class D)
• given in conjunction with some β-lactams:
  
  • ampicillin, amoxicillin, ticarcillin, piperacillin

Question 25

Brand names of β-lactam/β-lactamase drug combinations:

Answer 25

1. Augmentin®: amoxicillin + clavulanate (​​oral)
   
   • Staph. (MSSA)
   • E. coli, Klebsiella
   • Haemophilus, Moraxella
   • Proteus, Bacteroides (ampicillin/sulbactam)
2. Unasyn®: ampicillin + sulbactam
3. Timentin®: ticarcillin + clavulanate
4. Zosyn®: **piperacillin + tazobactam **(IV)
   
   • Staph. (MSSA)
   • E. coli, Klebsiella, Acinetobacter
   • Haemophilus
   • Bacteroides

Question 26

Cephalosporins:

Common Properties

Answer 26

1. well distributed to most areas of the body
   
   • only some reach the CSF
2. majority require injection
   
   • only some may be given orally
3. short half-lives (at best only a few hours)
4. mechanism: similar to other β-lactams
5. resistance mechanisms are comparable to those of penicillins

Question 27

List of Cephalosporins:

1. 1^st generation:
2. 2^nd generation:
3. 3^rd generation:
4. 4^th generation:

Answer 27

1. 1^st generation:
   
   • **cefazolin **
   • cephalexin
2. 2^nd generation:
   
   • ​​cefuroxime
   • cefoxitin
3. 3^rd generation:
   
   • ​​ceftriaxone
   • ceftazidime
4. 4^th generation:
   
   • ​​cefepime

Question 28

Use of 1^st generation Cephalosporins:

Answer 28

• mostly effective against gram-pos.
• limited gram-neg. activity
  
  • e.g. limited UTI use for some E. coli, Proteus
• surgical prophylaxis for skin flora

Examples

• cefazolin: best gram-pos. activity of cephalosporins
• cephalexin: oral

Question 29

Examples of 2^nd generation Cephalosporins:

Answer 29

• increased gram-neg. activity
  
  • incl. Haemophilus influenzae
• less active against staphylococci
• good tolerance to many gram-neg beta-lactamases

Examples

1. cefuroxime:
   
   • only 2nd generation to penetrate CSF
   • best of 2nd generation against Haemophilus
   • not the best against Enterics
2. cefoxitin:
   
   • also good for anaerobes, including Bacteroides fragilis

Question 30

Examples of 3^rd generation Cephalosporins:

Answer 30

• more active against gram-negs:
  
  • good for Klebsiella, Enterobacter, Proteus, Providencia, Serratia, Haemophilus
  • some effective against Ps. aeruginosa (e.g. ceftazidime)
• less effective against staphylococci
• some are for anaerobes
• stable against many gram-neg β- lactamases

Examples:

1. ceftriaxone:
   
   • therapy of choice for gonorrhea
   • empiric therapy for meningitis
   • long t_1/2 (~6–9 hrs)
2. ceftazidime:
   
   • effective against many strains of Ps. aeruginosa
   • shorter t_1/2 (~90 min )

Question 31

4^th generation Cephalosporins:

Answer 31

cefepime:

• IV, t_1/2 = 2 hr
• will penetrate CSF
• spectrum similar to ceftazidime
  
  • except more resistant to type I β-lactamases
• empirical treatment of serious inpatient infections

Question 32

None of the cephalosporins are good choices for:

Answer 32

1. Enterococcus
2. some strains of penicillin-resistant Strep. pneumoniae
3. methicillin-resistant Staph. (MRSA)
4. Listeria
5. Acinetobacter
6. Campylobacter jejuni
7. Legionella
8. Clostridium difficile

Question 33

Cephalosporins:

• Exceretion/Metabolism:
• Side Effects:

Answer 33

1. Excretion/metabolism:
   
   • renal clearance by glomerular filtration and tubular (anion) secretion
2. Side Effects:
   
   • allergic reactions
     
     • cross-reactions in 1–20% of patients with penicillins
   • nausea, vomiting, diarrhea, enterocolitis
   • hepatocellular damage

Question 34

Cephalosporins exhibit cross-allergies with __________.

Answer 34

penicillins

Question 35

Other ß-lactams (2):

Answer 35

carbapenems, monobactams

1. Imipenem
2. Aztreonam

Question 36

What are ESBLs? How are they treated?

Answer 36

Extended Spectrum β-Lactamases

• gram-negative species
• Inactivate penicillins and other drugs considered β-lactamase resistant:
  
  • 3rd gen. cephalosporins
• ceftriaxone, ceftazidime, cefotaxime, etc.
  
  • Monobactams (aztreonam)
• Carbapenems have become treatment of choice for ESBL organisms

Question 37

Imipinem (Primaxin®):

• Spectrum:
• Therapeutic Use:
• Side Effects:

Answer 37

• administered IV, well distributed
• broad spectrum:
  
  • several gram-pos. and gram-neg, aerobes and anaerobes
  • resistant to many β-lactamases, incl ESBLs
  • not effective against methicillin-resistant staphylococci
  • given with cilastatin, a renal peptidase inhibitor
    
    • extends t_1/2
    • some pseudomonads susceptible to hydrolysis by renal dipeptidases
• Uses:
  
  • mixed or ill-defined infection
  • those not responsive or resistant to other drugs
• Side Effects:
  
  • hypersensitivity
    
    • some cross-allergies with penicillins/ cephalosporins
  • seizures, dizziness, confusion
  • nausea, vomiting, diarrhea, pseudomembranous colitis
  • superinfection

Question 38

Aztreonam (Azactam®):

Answer 38

• used against gram-neg. aerobic rods
  
  • some Enterobacteriaceae, Haemophilus
  • some Pseudomonas aeruginosa
• not useful against gram-positives and anaerobes
• **resistant to many β-lactamases **
• used in those with known hypersensitivities to penicillins
• given IM or IV, well distributed, incl. CSF
  
  • not indicated for meningitis
• some adverse effects:
  
  1. seizures, confusion, weakness, etc.
  2. cramps, nausea, vomiting, enterocolitis
  3. anaphylaxis, transient EKG changes
  4. hepatitis, jaundice

Question 39

Vancomycin (Vancocin®):

Mechanism:

Answer 39

Glycopeptide antibiotic, not a β-lactam

• bactericidal (slower than β-lactams)
• inhibits cell wall synthesis:
  
  • binds to free carboxyl end (D-Ala-D-Ala) of the pentapeptide
• interferes with transpeptidation (cross-linking) and transglycosylation (elongation of the peptidoglycan chains)
• may also disrupt cell membranes and inhibit RNA synthesis

Question 40

Vancomycin:

Uses

Answer 40

gram-positives ONLY, including:

1. methicillin-resistant Staphylococcus (MRSA), and MSSA
2. hemolytic Streptococcus, S. pneumoniae (incl. penicillin-resistant),
3. Enterococcus
4. staphylococcal or streptococcal endocarditis
5. Clostridium, Corynebacterium, coagulase-neg. staph., Listeria, etc.
6. Clostridium difficile enterocolitis (2nd choice)
7. Empiric treatment for meningitis
   
   • 3rd generation cephalosporin + vancomycin

Question 41

Vancomycin:

Administration

Answer 41

• must be given IV for systemic infections
• oral form effective for Clostridium difficile enterocolitis
• primarily used in serious infections, incl. those allergic to penicillins
  
  • limited penetration into CSF and only when meninges are inflamed

Question 42

Vancomycin:

Side Effects

Answer 42

1. “red man” or “red neck” syndrome
   
   • head and neck erythema
2. nephrotoxicity, esp. with patients also receiving aminoglycosides
3. phlebitis
   
   • avoided by using dilute solutions & slow infusion
4. ototoxicity
   
   • usually only with other ototoxic drugs
   • e.g. aminoglycosides

Question 43

Fosfomycin (Monurol®):

• Mechanism:
• Use:
• Toxicity:​​

Answer 43

1. Mechanism:
   
   • inhibits synthesis of peptidoglycan building blocks by inactivating enolpyruvyl transferase, an early-stage cell wall synthesis enzyme
   • blocks condensation of UDP-N-acetylglucosamine with phosphoenolpyruvate
2. Use:
   
   • uncomplicated UTIs
     
     • caused by E. coli, Enterococcus
   • single oral dose maintains effective urinary concentration for 3 days
3. Toxicity: headache, diarrhea, nausea, vaginitis dizziness, rash

Question 44

Bacitracin:

1. Mechanism:
2. Use:
3. Toxicity:

Answer 44

Polypeptide, not a β-lactam

1. Mechanism:
   
   • interferes with cell wall synthesis by interfering with lipid carrier that exports early wall components through the cell membrane
2. Use: Topical use only
   
   1. very nephrotoxic so is rarely used internally
   2. gram-positive spectrum
3. Toxicity: allergic dermatitis with topical use

Question 45

Drugs that Target Cell Membrane:

Answer 45

1. Polymyxins:
   
   • Polymyxin B
   • Polymyxin E (colistin)
2. Cyclic lipopeptides:
   
   • Daptomycin

Question 46

Polymyxin B (Aerosporin®):

Answer 46

• topical use
  
  • esp. for Pseudomonas and other gram-neg. infections
• gram-neg spectrum
• rare IM or intrathecal use for SERIOUS gram-neg. infections, incl. Ps. aeruginosa
• Side Effects:
  
  • topical use – few problems
  • systemic use – potential for serious nephrotoxicity and neurotoxicity

Question 47

Daptomycin (Cubicin™)**: **

Mechanism

Answer 47

• binds to bacterial cytoplasmic membrane, causing rapid membrane depolarization
• Rapidly bactericidal

Question 48

**Daptomycin: **

Use

Answer 48

• complicated skin and skin structure infections:
  
  • Staph. aureus (MSSA, MRSA)
  • Streptococcus pyogenes and agalactiae
  • Enterococcus (vancomycin-susceptible only)
• also for Staphylococcus bacteremia
• NOT for pneumonia

Question 49

**Daptomycin: **

Side Effects

Answer 49

• nausea, diarrhea, GI flora alterations
• muscle pain and weakness
  
  • ​monitor CPK levels
• fever, headache, rash, dizziness, injection site reactions

Question 50

Drugs that Target Nucleic Acids:

Answer 50

1. Quinolones
   
   • Fluorinated:
     
     • Norfloxacin, ciprofloxacin, moxifloxacin
   • Non-fluorinated
2. Nitrofurantoin
3. Rifampin
4. Metronidazole

Question 51

Quinolones:
Mechanism

Answer 51

• inhibits α (and possibly β) subunit of DNA gyrase, thereby interfering with control of bacterial DNA winding (replication and repair)
• bactericidal
  
  • killing dependent on AUC_24hr/MIC

Question 52

**Quinolones: **

Resistance

Answer 52

• altered DNA gyrase
  
  • fluorinated quinolones are still effective
• combination of decreased permeability (e.g. altered outer membrane porins) and altered DNA gyrase
  
  • result in resistance to the newer fluorinated compounds

Question 53

Quinolones:

Administration

Answer 53

• some IV; oral
  
  • antacids and H2 blockers might decrease absorption
• fluorinated quinolones are well-distributed, incl. the CSF
• nonfluorinated agents achieve therapeutic concentrations only in the urinary tract

Question 54

What are the nonfluorinated quinolones used for?

Answer 54

nalidixic acid, oxolinic acid, cinoxacin

• Enterobacteriaceae in urinary tract

Question 55

Norfloxacin (Chibroxin®, Noroxin®):

Answer 55

• urinary tract infections:
  
  • Enterobacteriaceae
  • some Pseudomonas aeruginosa, Staphylococcus, and Enterococcus
• not useful for many sites

Question 56

Ciprofloxacin (Cipro®):

Answer 56

useful for infections at many sites

1. urinary tract infections (similar spectrum to norfloxacin)
2. infectious diarrhea (Shigella, Campylobacter jejuni,
   enterotoxigenic E. coli, some Salmonella)
3. bone and joint infections (Enterobacter, Serratia, some Ps. aeruginosa)
4. skin infections (Enterobacteriaceae, some Ps. aeruginosa)
5. Chlamydia

• Ciprofloxacin itself is not the best choice for gram-pos. infections
  
  • ​cannot achieve the correct AUC_24hr/MIC ratio
• Other quinolones have better gram-pos. and respiratory activity (e.g. moxifloxacin)

Question 57

Moxifloxacin (Avelox®):

Answer 57

• better gram-pos. activity than many quinolones
  
  • but still targets some gram-negs.
• respiratory infections, but not for Strep. throat:
  
  • Strep. pneumoniae, Mycoplasma, Haemophilus, Moraxella, Klebsiella, MSSA
  • community-acquired pneumonia, bacterial bronchitis, sinusitis
  • Legionella (levofloxacin)

Question 58

Quinolones:

Side Effects

Answer 58

1. nausea, vomiting, abdominal pain, enterocolitis
2. dizziness, headache, restlessness, depression (1-11%)
3. rare seizures
4. rashes, photosensitivity (2%)
5. EKG irregularities, arrhythmias
   
   • e.g., prolonged QTc interval
6. arthropathy and tendon rupture
7. peripheral neuropathy
8. precautions:
   
   • seizure disorders
   • pregnancy category C
   • children (possible cartilage damage)

Question 59

Nitrofurans:

Answer 59

Nitrofurantoin

Question 60

Nitrofurantoin:

• Mechanism:
• Use:

Answer 60

• Mechanism:
  
  • ​nitroreductase enzyme converts them to reactive compounds (incl. free radicals) which can damage DNA
• ​Use:
  
  • urinary tract infections (lower UTI only)

Question 61

Nitrofurantoin:

Side Effects

Answer 61

1. nausea, vomiting, diarrhea
2. peripheral neuropathy
3. hypersensitivity, fever, chills
4. acute and chronic pulmonary reactions:
   
   • fever, cough, dyspnea
5. may cause peroxidative damage to pulmonary membrane lipids
6. acute and chronic liver damage
7. granulocytopenia, leukopenia, megaloblastic anemia
8. acute hemolytic anemia
   
   • glucose-6-P dehydrogenase deficiency

Question 62

Rifampin (rifampicin):

1. Mechanism​:
2. Use:

Answer 62

1. Mechanism
   
   • inhibits bacterial RNA synthesis by binding RNA polymerase β
   • bactericidal
2. ​Use
   
   • very lipophilic
   • primarily for treatment of pulmonary tuberculosis
   • **Prophylaxis treatment for: **
     
     • meningococcal meningitis
     • Haemophilus influenza type b meningitis

Question 63

Rifampin:

Side Effects

Answer 63

• serious hepatotoxicity (<1%)
• rifampin strongly induces hepatic enzymes (many CYPs) that inactivate other drugs
  
  • CYP1A, 2A, 3A, 2B, 2C9, 2C19
  • (e.g. β-blockers, barbiturates, sulfonylureas, corticosteroids, digitalis, oral contraceptives, anticoagulants, quinidine, phenytoin, others)
• orange color (urine, saliva, tears, sweat)

Question 64

Fidaxomicin (Dificid®):

1. Mechanism:
2. Administration:
3. Use:
4. ​Side Effects:

Answer 64

1. Mechanism
   
   • ​​noncompetitive inhibitor of RNA polymerase, ⇒ inhibiting RNA synthesis
   • bactericidal
2. ​Administration
   
   • oral, poorly absorbed
3. Use
   
   • ​​C. difficile infection (3rd line)
4. Side Effects
   
   • ​​GI upset (4–10%) (nausea, vomiting, diarrhea)
   • GI bleeding (4%)

Question 65

Metronidazole (Flagyl®, Metrogel®):

1. ​Mechanism:
2. Use:

Answer 65

1. Mechanism:
   
   • anaerobes reduce the nitro group of metronidazole
   • resulting product disrupts DNA and inhibits nucleic acid synthesis
   • bactericidal
2. Use:
   
   • anaerobes
   • Clostridium difficile enterocolitis (mild/moderate cases)
   • prevent infection after colorectal surgery
   • combination therapy for Helicobacter pylori
   • Gardnerella vaginalis

Question 66

**Metronidazole: **

Side Effects

Answer 66

1. nausea, vomiting, anorexia, diarrhea
2. transient leukopenia, neutropenia
3. thrombophlebitis after IV infusion
4. bacterial and fungal superinfections
   
   • esp. Candida

Question 67

What can cause C. Difficile enterocolitis?

Answer 67

• Can be caused by all antibacterials
• Incidence increasingly rapidly, epidemic proportions
• Severity: from diarrhea to life-threatening colitis
• Consider in all patients with antibacterial drugs in last 2 months
  
  • Some cases now in drug-naïve
• Diagnosis usually by C. difficile toxin in stool (look for toxins A, B)

Question 68

How is C. Difficile enterocolitis treated?

Answer 68

Therapy:

• Fluid/electrolytes
• Protein supplementation
• Possible surgery

Antibacterials:

• Metronidazole (1st choice, esp. for mild-to-moderate cases)
  
  • Hypertoxigenic strains may be less susceptible to metronidazole
• Vancomycin (better for mod.-to-severe cases)
• Vancomycin + metronidazole (very severe cases)
• Fidaxomicin