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®)**:** ## Footnote **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™)**: ** ## Footnote **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**