Module 2 (of 3): Antibiotic Review*

1
Module 2 (of 3) Antibiotic Review
Review of selected antimicrobials By Keith
Teelucksingh, PharmD Infectious Disease
Pharmacist, Kaiser Permanente Vallejo With
contributions by Linh Van, PharmD Infectious
Disease Pharmacist, Kaiser Permanente Oakland
?See Notes
2
Goals

• Build upon pharmacists basic knowledge of
  selected broad-spectrum antibiotics
• Provide contemporary clinical information on
  appropriate use, spectrum of activity, clinical
  pearls and other considerations of selected
  antibiotics.

3
Objectives

• Upon completion of this module, the participant
  will be able to
• Elaborate on the spectrum activity for the
  ß-lactam-related antibiotics, aztreonam,
  vancomycin, clindamycin, metronidazole and the
  fluoroquinolones
• Discuss the appropriate clinical uses of the
  broad spectrum ß-lactam-related antibiotics and
  vancomycin

4
Objectives

• Describe the appropriate use of the
  anti-anaerobic agents clindamycin and
  metronidazole when combined with other
  anaerobically active antibiotics
• Describe the appropriate use of ß-lactam agents
  and vancomycin agents for the treatment of
  certain bacteria

5
Antibiotics to be Covered

• Other
• Clindamycin
• Metronidazole
• Vancomycin

• ß-Lactams
• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams
• Aztreonam
• Quinolones
• Moxifloxacin
• Ciprofloxacin

6
Adapted from Brett Heintz, PharmD, BCPS
7
ß-Lactams

• Natural penicillins penicillin
• Penicillinase-resistant penicillins nafcillin,
  dicloxacillin
• Aminopenicillins ampicillin, amoxicillin
• Extended spectrum penicillins pipercillin,
  ticarcillin
• ß-lactam/ß-lactamase inhibitor combinations
• Zosyn, Unasyn, Augmentin, Timentin

8
Penicillins

• Penicillin G (IV)
• Used for treatment of
• Neurosyphilis, endocarditis due to susceptible
  pathogens
• Infections due to penicillin (PCN) susceptible
  (S) organisms Group A B Streptococci,
  Clostridium perfringes (gas gangrene)
• If organism is PCN S (does not produce
  penicillinase, e.g., Staphylococcus aureus)
  penicillin, amoxicillin, ampicillin can all be
  used

9
Penicillins

• Penicillin G
• Side effects
• Allergic reactions (rash, blood dyscrasias,
  anaphylaxis) -gt discussed in more detail in
  Module 3
• Interstitial nephritis
• Hyperkalemia
• Phlebitis

10
Penicillins

• Nafcillin
• Coverage Staphylococcus aureus (MSSA) ? drug of
  choice
• Not as active versus other Gm
• Does not cover Enterococcus, not as good as
  penicillin for S. pneumoniae, S. pyogenes
• Hepatobiliary clearance
• No need to adjust in renal dysfunction
• Note Even though nafcillin is not renally
  eliminated, it still can cause interstitial
  nephritis

11
Penicillins

• Nafcillin
• When interpreting susceptibilities
• oxacillin nafcillin
• Susceptibility to nafcillin predicts
  susceptibility to cefazolin/cephalexin

12
Penicillins

• Nafcillin
• Side Effects
• Interstitial nephritis
• Still monitor serum creatinine if on long course
• Neutropenia
• Usually seen with longer courses
• Phlebitis
• Usually occurs when given peripherally
• Use central venous catheter or isotonic solution

13
Penicillins

• Ampicillin/amoxicillin
• Drug of choice for Enterococcus spp. infections
• If isolate is ampicillin/amoxicillin sensitive
• Amoxicillin (PO)
• Higher dose used for S. pneumoniae (otitis media,
  pharyngitis)
• Enterococcal UTI
• Ampicillin (IV)
• Serious infections due to Enterococcus spp.
• Listeria (unpasteurized cheeses) infections ?
  typically added for coverage in meningitis

14
Penicillins

• Ampicillin clinical applications
• Endocarditis/bacteremia
• Ampicillin 2g IV q 4h
• No one agent is bactericidal against Enterococcus
  spp.
• Bactericidal when combined with aminoglycoside
  (AG)
• If treating endocarditis, addition of AG is
  strongly recommended
• Formal ID consult recommended

15
Penicillins

• Pharmacokinetic considerations
• Bioavailability (oral)
• Amoxicillin, Dicloxacillin gt Ampicillingt PCN VK
• High concentration in urine
• All need to be adjusted in renal dysfunction
• Exceptions nafcillin, dicloxacillin

16
Penicillins

• Ampicillin/amoxicillin
• Side effects (in general, similar to penicillin)
• Allergic reactions
• Rash
• Eosinophilia
• Leukopenia

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Extended Spectrum Penicillins

• Piperacillin
• Good activity vs. Pseudomonas and Enterococcus
• Less active vs. E. coli
• TicarcillinNF
• Good activity vs. Pseudomonas (alternative to
  piperacillin)
• Less active than piperacillin vs. Enterococcus
• Not commercially available

NF non formulary
? See Notes
18
ßL/ßLi combinations

• Unasyn (ampicillin/sulbactam)
• Augmentin (amoxicillin/clavulanic acid)
• Zosyn (piperacillin/tazobactam)
• Timentin (ticarcillin/clavulanic acid) NF
• ßL/ßLi ß-lactam/ß-lactamaseinhibitor
• NF non-formulary

19
ßL/ßLi combinations

• All will cover ampicillin-sensitive Enterococci
• All have excellent activity vs. anaerobes
• B. fragilis, Prevotella spp.
• Unasyn and Augmentin do not cover Pseudomonas
• Addition of ßLi adds activity against
• Bacteroidies (anaerobes), ß-lactamase producing
  Gm (E. coli, Klebsiella, Serratia) Gm
  (Enterococci, MSSA)

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ßL/ßLi combinations

• Unasyn (ampicillin/sulbactam)
• Good for Gm
• MSSA/Strep spp./Enterococcus spp.
• Uses Diabetic foot ulcers, cellulitis,
  community- acquired pneumonia, mild
  community-acquired GI infections (diverticulitis)
• Variable Gm - coverage
• E. coli has high resistance
• Best in class for Acinetobacter (if isolate S)

?See Notes
21
ßL/ßLi combinations

• Augmentin (amoxicillin/clavulanic acid)
• Gram coverage similar to Unasyn
• Sometimes more active versus Gram pathogens
  such as E. coli and Klebsiella spp. than Unasyn
• Only PO option in class
• GI tolerance poor
• Uses diverticulitis, cellulitis
• Good oral step-down therapy

22
ßL/ßLi combinations

• Zosyn (piperacillin/tazobactam)
• Expanded coverage compared to Unasyn
• Similar to Timentin? may be slightly more active
  versus certain bacteria (E. coli)
• Good activity vs. Pseudomonas
• The addition of tazobactam to piperacillin adds
  NO extra activity vs. Pseudomonas
• For confirmed pseudomonal infections, increase
  dose to 4.5g IV q6h (renal function permitting)
  to maximize its pharmacodynamic properties vs.
  Pseudomonas

23
ßL/ßLi combinations

• Zosyn (piperacillin/tazobactam)
• Clinical uses severe intra-abdominal infections,
  health care-associated (HCA) infections,
  including pneumonia/ventilator-associated
  pneumonia
• Use should be reserved for patients with risk
  factors for nosocomial/drug resistant pathogens
• Skilled nursing facility residents, previous
  antibiotics exposure, exposure to health care
  environment, immunocompromised patients

?See Notes
24
ßL/ßLi combinations

• Timentin (ticarcillin/clavulanicacid)NF
• Per previous slide, very similar coverage
  compared to Zosyn
• May be used as alternative agent for infections
  due to Stenoptrophomonasmaltophilia
• NF non-formulary

25
ßL/ßLi combinations

• Side effects overall, very similar to
  penicillins
• Zosyn
• Thrombocytopenia has been seen with longer
  courses of therapy and higher doses (i.e.,
  Pseudomonal dosing)
• Ticarcillin/Timentin
• Ticarcillin has been shown to impair platelet
  function ? may prolong bleeding time but unclear
  whether this is clinically significant

26
Carbapenems

• The most potent antibiotic in theß-lactam class
• These agents should be used only when no other
  antibiotic options are available or appropriate
• Meropenem (Merrem)
• Ertapenem (Invanz)
• Imipenem/cilastin (Primaxin) NF
• Doripenem (Doribax) NF

NF non-formulary
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Carbapenems

• Spectrum of activity
• Broadest coverage including Gm, Gm- (especially
  drug resistant species -gt see below and notes),
  anaerobic coverage
• All cover MSSA, Enterococcus (ampicillin
  sensitive), Streptococcus spp.
• Drugs of choice for ESBL infections
• Good empiric coverage for Acinetobacter,
  Citrobacter, Pseudomonas
• - except ertapenem

? See Notes
28
Carbapenems

• Differences in spectrum of activity
• Imipenem meropenem
• Meropenem usually has lower minimum inhibitory
  concentration (MIC) to Gm - pathogens ? not
  usually clinically significant
• Ertapenem
• Not clinically active vs. Enterococcus,
  Pseudomonas, Acinetobacter
• Not a good empiric choice for health care
  associated infections

? See Notes
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Carbapenems

• Differences in spectrum of activity
• DoripenemNF
• Same coverage as meropenem/imipenem
• May be useful for highly multidrug-resistant
  organisms
• Lower MIC to certain pathogens in vitro
• Less likely to select for resistance in certain
  bacterial subpopulations
• At present, not much advantage over meropenem for
  most indications
• NF non-formulary

30
Carbapenems

• Clinical uses
• Severe intra-abdominal infections, heath
  care-associated infections including pneumonia,
  ventilator-associated pneumonia, serious
  infections due to ESBL-producing organisms,
  meningitis
• Use should be reserved for patients with risk
  factors for nosocomial/drug-resistant pathogens
  (see Zosyn slide)
• - except ertapenem - meropenem only

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Carbapenems

• Side effects
• Hypersensitivity/allergic reactions
• Uncommon
• Low cross-reactivity in patients with penicillin
  allergy (see Module 3 of this series)
• Seizures
• Usually associated with imipenem and occurs in
  patients with poor renal function where dose not
  adjusted accordingly, previous seizure history
  may also predispose

32
Carbapenems

• Drug interaction
• Valproic acid and meropenem? decreases valproic
  acid levels (may apply with all carbapenems).
• Monitor valproic acid levels more frequently or
  use alternative antibiotic.

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Monobactams

• Aztreonam (only drug in class, Azactam)
• Monocylic ß-lactam ring (traditional ß-lactams
  are bicyclic) i.e., structurally different
• Active against Gm - ONLY including Pseudomonas
• Gm coverage similar to ceftazidime (they have
  structurally similar side chains)
• Side effects rash
• Can be safely used in patients with Type I
  penicillin allergy
• Caution if patient has ceftazidime allergy (see
  Module 3)
• ? Currently on backorder use only when no other
  options are available

34
Program Learning

• What is the drug of choice for ampicillin-sensitiv
  e Enterococcus? Besides the drug of choice, what
  other beta-lactam(s) would work?
• Which penicillins cover MRSA?
• What are the penicillins that would cover MSSA?

35
Program Learning Answers

• What is the drug of choice for ampicillin
  sensitive Enterococcus? Besides the drug of
  choice, what other beta-lactam(s) would work?
• Ampicillin is the drug of choice. Amoxicillin,
  penicillin, piperacillin, ticarcillin, imipenem,
  meropenem would also be appropriate choices. No
  cephalosporin covers Enterococcus. Ertapenem has
  variable activity. Aztreonam has no gm coverage.

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Program Learning Answers

• Which penicillins cover MRSA? None. No ß-lactam
  agent covers MRSA.
• What are the penicillins that would cover MSSA?
  Nafcillin, dicloxacillin, Zosyn, Timentin,
  Augmentin, Unasyn. If isolate is
  PCN-susceptible (this indicates that isolate does
  not produce penicillinase), then also can use
  penicillin, amoxicillin or ampicillin.

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Program Learning Answers

• A patient with resistant Pseudomonas aeruginosa
  wound infection has been on meropenem in-house
  and the MD plans to give ertapenem as a home IV
  infusion. His rationale is that ertapenem is a
  once daily medication as opposed to three times
  daily for meropenem. Is this appropriate? Why?

38
Program Learning Answers

• Not appropriate because ertapenem does not cover
  Pseudomonas. The carbapenems with activity
  against Pseudomonas are imipenem, meropenem and
  doripenem.

39
Cephalosporins

• These compounds are structurally related to the
  penicillins due to presence of ß-lactam ring.
  This will only focus on cephalosporins used
  commonly in the inpatient setting
• 1st generation
• 2nd generation
• 3rd generation
• 4th generation

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Cephalosporins

• No cephalosporins cover Enterococcus
• No cephalosporins cover MRSA
• None are active versus ESBL-producing organisms
• All cephalosporins, including 3rd generation, are
  rendered inactive
• Cefepime still may be used for certain infections
  but should consult with ID clinician before using

41
Cephalosporins

• 1st generation
• Cefazolin (Ancef)
• Proteus, E. coli, Klebsiella (PEK), MSSA,
  Streptococcus spp.
• Better for Streptococcus spp. than nafcillin
  (cellulitis)
• Cephalexin (Keflex), cefadroxil (Duricef)
• Both with similar coverage to cefazolin
• Both are well absorbed orally
• Cefadroxil - less frequent dosing

42
Cephalosporins

• 1st generation
• Uses
• Cefazolin
• Cellulitis, MSSA infections, surgical prophylaxis
• Cephalexin, cefadroxil
• UTI, skin/soft tissue infections due to MSSA or
  Strep spp.

43
Cephalosporins

• 2nd generation
• Cefuroxime (PO/IV), cefaclor (PO)
• Coverage PEK (see 1st generation slide)
  Haemophilus, Neisseria HNPEK
• More gram negative coverage, less Staph coverage
• Cephamycins (IV) cefotetan, cefoxitin
• Only cephalosporins that cover anaerobes
• Both active vs. B. fragilis ? be aware that
  resistance is increasing
• Used for pelvic inflammatory disease, surgical
  prophylaxis in ObGyn and colorectal surgery

44
Cephalosporins

• 3rd generation
• Ceftriaxone (Rocephin), cefotaxime (IV only)
• HNPEK Serratia HNPEKS
• Not as reliable for Staph
• Good Pneumococcus activity, good meningeal
  penetration
• Multiple uses UTI, SBP, meningitis, pneumonia
• Cefpodoxime, cefdinir, cefixime (all PO)
• Cefixime use should be reserved for treatment of
  STDs

45
Cephalosporins

• 3rd generation
• Ceftriaxone
• Has numerous indications but only a few require
  doses higher than 1g
• 2g IV q24h (endocarditis and osteomyelitis)
• 2g IV q12h (meningitis)
• No adjustment needed for renal dysfunction

46
Cephalosporins

• 3rd generation
• Ceftazidime (Fortaz)
• Coverage is broadened compared with others in 3rd
  generation to include Pseudomonas
• Only other cephalosporin which covers Pseudomonas
  is cefepime
• Not so good for Staphylococcus, Streptococcus
• Used for empiric treatment of febrile
  neutropenia, has decent meningeal penetration

47
Cephalosporins

• 4th generation
• Cefepime (Maxipime)NF
• Similar to ceftazidime, covers Pseudomonas and
  may be slightly more active vs. some Gm
  organisms
• Better Gm coverage than ceftazidime but still
  not as good as 1st generation cephalosporins
• Used in febrile neutropenia, health
  care-associated infections, meningitis
• May be used in certain infections/situations when
  treating ESBL infections ?consult ID clinician
• NF non-formulary

48
Cephalosporins

• Side effects
• Similar to penicillins
• Allergic reactions
• Blood dyscrasias
• Rare

49
Program Learning

• Which cephalosporins do not need renal
  adjustment?
• How is ceftriaxone dosed for these disease
  states?
• Community-acquired pneumonia, endocarditis,
  osteomyelitis, meningitis
• Which cephalosporins have anaerobic coverage?
• Which cephalosporins cover Pseudomonas?

50
Program Learning Answers

• Which cephalosporins do not need renal
  adjustment? Ceftriaxone only. All other
  cephalospsorins need to be adjusted for renal
  dysfunction.
• How is ceftriaxone dosed for these disease
  states? CAP 1g iv q24h, Endocarditis/Osteomyeliti
  s 2g iv q24h, Meningitis 2g iv q12h

51
Program Learning Answers

• Which cephalosporins have anaerobic coverage?
  Cefoxitin and cefotetan both are 2nd generation
  cephalosporins.
• Which cephalosporins cover Pseudomonas?
  Ceftazidime and cefepime.

52
Fluoroquinolones

• These are potent antibiotics that have excellent
  oral bioavailability
• Ciprofloxacin
• Moxifloxacin
• LevofloxacinNF
• Trovafloxacin (off market - hepatotoxic)
• Gatifloxacin (off market - dysglycemias)
• NF non-formulary

53
Fluoroquinolones

• Good options for certain disease states
• Moxifloxacin in CAP
• Used as second-line treatment for Tuberculosis
  (TB)
• If presenting with upper lobe pneumonia and TB
  suspected, do NOT give a quinolone
• Overuse has lead to increased resistance
• While the fluoroquinolones are potent
  antibiotics, bacteria have the capacity to
  rapidly develop resistance to these agents,
  especially under repeated exposure

? See Notes
54
Fluoroquinolones

• Excellent oral bioavailability
• Use should be reserved for cases where other
  agents cannot be used
• i.e., patients with severe penicillin allergy
• If an isolate is resistant to one quinolone,
  consider it resistant to all quinolones
• Only drug in class with anaerobic activity is
  moxifloxacin

55
Fluoroquinolones

• Ciprofloxacin
• Limited Gm activity
• Poor S. pneumoniae coverage
• Active against Enterobacteraciae, Pseudomonas
• Resistance rates will vary per institution, get
  an idea of antibiogram/susceptibilities at your
  area of practice
• Can be used for Enterococcus spp. UTIs
• If isolate susceptible, do not use for any other
  type of Enterococcus infection (i.e., bacteremia)

56
Fluoroquinolones

• LevofloxacinNF
• S. pneumoniae coverage is better than
  ciprofloxacin but not as good as moxifloxacin
• Has activity versus Enterobacteriaciae,
  Pseudomonas
• Not much advantage over ciprofloxacin for most Gm
  - pathogens
• NF non-formulary

57
Fluoroquinolones

• Moxifloxacin
• Coverage
• Most active fluoroquinolone for S. pneumoniae
• Excellent anaerobic coverage -gtB. fragilis
• Similar Gram activity compared to other
  fluoroquinolones but no activity vs. Pseudomonas
• Uses
• Community-acquired pneumonia, intra-abdominal
  infections
• No need for renal adjustment

58
Fluoroquinolones

• Drug interactions
• Divalent/trivalent containing products (Ca2,
  Mg2, Al3, antacids)
• Can decrease oral absorption up to 90 percent,
  similar effect with tube feeds
• Concentration dependent antibiotics so need to
  treat interactions that ? bioavailability
  seriously
• Administer separately per manufacturer
  recommendation

59
Fluoroquinolones

• Drug Interactions
• Warfarin
• Increased INR, risk of bleeding
• Cardiac meds
• Caution when used with other meds that can
  prolong QTc interval
• Consult package information for other
  interactions

60
Fluoroquinolones

• Side effects
• CNS ? more common in elderly
• Interstitial nephritis
• Rare
• QTc prolongation
• Cartilage toxicity
• Precaution in very young and elderly
• N/V/D
• Most common side effect

61
Program Learning

• A patient has been admitted for
  community-acquired pneumonia, placed on
  ceftriaxone and azithromycin, and is doing well.
  Upon discharge, which antibiotic would you
  recommend?
• A patient is admitted for suspected pneumonia
  from home. The chest X-ray shows right upper lobe
  lesion. Patient also has a three-week history of
  weight loss and night sweats and a history of
  PPD test. What antibiotic class would you want to
  avoid and why?

62
Program Learning Answers

• The patient has been admitted for
  community-acquired pneumonia, placed on
  ceftriaxone and azithromycin, and is doing well.
  Upon discharge, which antibiotic would you
  recommend? Moxifloxacin. This is a recommended
  therapy in the CAP guidelines.

63
Program Learning Answers

• A patient is admitted for suspected pneumonia
  from home. The chest X-ray shows right upper lobe
  lesion. Patient also has a three-week history of
  weight loss and night sweats and a history of
  PPD test. What antibiotic class would you want to
  avoid and why? Fluoroquinolones, especially newer
  generations like moxifloxacin. These have
  activity against TB and can potentially mask
  infection by partially treating it.

64
Clindamycin

• Spectrum of activity
• S. aureus ? check sensitivities of isolate before
  using, Strep spp.
• Was once highly active against anaerobic gut
  bacteria but resistance has been increasing
  through the years
• Still has relatively good activity against oral
  flora anaerobic species
• No appreciable Gm - activity

65
Clindamycin

• Role/clinical uses
• Used in combination with other antibiotics for
  necrotizing fasciitis to decrease toxin
  production from bacteria (Strep spp.)
• Ribosomal binding prevents production of
  destructive proteins
• Used in combination with other anaerobically
  active antibiotics for this disease state

66
Clindamycin

• Role/clinical uses
• Still used frequently for dental infections,
  surgical prophylaxis
• Especially in patients with penicillin allergy
• Commonly used as prophylaxis/treatment in head
  and neck procedures
• Poorly GI tolerated, may predispose patients to
  C. difficile colitis

67
Metronidazole

• Spectrum of activity
• Only covers anaerobic bacteria ? very little
  resistance, excellent activity
• Gram () and Gram (-) anaerobes
• Bacteriodes spp.
• Prevotella spp.
• Clostridium spp. (including C. difficile)
• Fusobacterium spp.
• Covers some parasitic organisms as well

68
Metronidazole

• Used in
• C. difficile colitis
• Infections where anti-anaerobic coverage is
  desired or used in combination with other
  antibiotics which do not have anaerobic activity
• Surgical prophylaxis (colorectal, vaginal,
  abdominal)
• Bacterial vaginosis, trichomoniasis

69
Metronidazole

• Treatment of C. difficile colitis
• Still first-line agent for uncomplicated,
  mild-moderate cases
• If severe case (definitions of severity may
  differ), PO vancomycin usually used
• IV metronidazole can be used to treat but not
  optimal (PO route will get highest concentration
  to area of infection)

70
Metronidazole

• Drug interactions
• Warfarin
• Increased INRs, consider using PO vancomycin
• Lithium
• EtOH
• Disulfiram-like reaction with EtOH
• Side effects
• Metallic taste, dark urine

71
Double Anaerobic Coverage

• There is no need to add extra anaerobic coverage
  (in the form of clindamycin or metronidazole) to
  antibiotics with anaerobic coverage
• There are consequences in gut colonization
• It is redundant and unnecessary
• - Carbapenems, ßL/ßLi combos, moxifloxacin,
  tigecycline

?See Notes
72
Double Anaerobic Coverage

• It may be appropriate to have double anaerobic
  coverage in these situations
• Adding metronidazole to anaerobically active
  antibiotics for treatment of C. difficile
  diarrhea.
• Should be stopped promptly if C. difficile assay
  is negative
• Adding clindamycin to anaerobically active
  antibiotics for treatment of necroitzing fasciitis

73
Program Learning

• What is the spectrum of activity for clindamycin?
• A patient with Serratia bacteremia is started on
  clindamycin. What is wrong with this?
• A patient with hospital-acquired pneumonia, on
  Zosyn, is started on metronidazole. Under what
  circumstance would this be appropriate?

74
Program Learning Answers

• What is the spectrum of activity for clindamycin?
  Anaerobic bacteria, check sensitivities before
  using for either Staphylococci and Streptococci.
• A patient with Serratia bacteremia is started on
  clindamycin. What is wrong with this?
  Clindamycin has no appreciable Gm activity.

75
Program Learning Answers

• A patient with hospital-acquired pneumonia, on
  Zosyn, is started on metronidazole. Under what
  circumstance would this be appropriate?
• If patient has diarrhea and C. difficile is
  suspected (stool sample should be sent for C.
  difficile tests). Otherwise Zosyn has excellent
  anaerobic activity.

76
Vancomycin

• Inhibits cell wall synthesis, bactericidal.
• Crosses blood-brain barrier if inflamed.
• Spectrum Gm ONLY
• MRSA, Enterococcus, Coagulase Negative Staph
  spp., Strep spp.
• Clostridium difficile (when used via oral route).

77
Vancomycin

• Delayed killing against S. aureus and MRSA ?
  especially with high inoculum size (in vitro).
• If S. aureus isolate is ß-lactam sensitive
  (i.e MSSA), use ß-lactam antibiotic ? better
  killing, better outcomes.

78
Vancomycin

• Still considered by many the drug of choice vs.
  MRSA but is a controversial issue.
• Issues with increasing Staph MICs, PK/PD issues,
  suboptimal clinical responses have all led to
  question vancomycin as first-line therapy.
• Newer drugs and new studies have also raised
  questions.
• Ongoing and controversial issue.

79
Vancomycin

• Dosing and monitoring Please see institutional
  protocol as dosing, frequency of monitoring and
  goal trough level ranges may differ between
  facilities.
• Review the recent consensus statement on
  vancomycin monitoring.
• - Rybak M, et al. 2009.

80
Vancomycin

• Side effects
• Nephrotoxicity with other nephrotoxic drugs.
• Redmans Syndrome
• This is an infusion-related reaction.
• Slow infusion rate if occurs (infuse over two
  hours) may use diphenhydramine for symptomatic
  relief.
• Blood dyscrasias
• Neutropenia, thrombocytopenia.
• Tend to be seen during longer treatment courses.

81
Vancomycin

• Clinical uses
• Serious infections where MRSA is suspected.
• Therapy for Gm infections in patients with
  serious allergic reactions to ß-lactam
  antibiotics.
• Treatment for C. difficile colitis (given PO).
• Systemic infections cannot be treated with
  vancomycin PO ? localized to gut.

82
Vancomycin

• Clinical uses
• If initial cultures do not show MRSA, prescriber
  should be contacted to review appropriateness
• If not indicated, vancomycin should be
  discontinued as quickly as possible to avoid
• pressure for the development of VRE or selection
  of other resistance
• potential toxicities
• unnecessary use of powerful antibiotic

83
Program Learning

• Patient with MSSA leg infection on vancomycin IV.
  Patient has no allergies. Is there a better
  antibiotic?
• True/false. Vancomycin is bactericidal.
• An order is written to use high-dose PO
  vancomycin to treat a MRSA cellulitis. Is this
  appropriate?

84
Program Learning Answers

• Patient with MSSA leg infection on vancomycin IV.
  Patient has no allergies. Is there a better
  antibiotic? Yes. The ß-lactams have better
  killing activity vs. MSSA than vancomycin.
  Nafcillin, dicloxacillin and cephalexin are
  potential options.
• True/False. Vancomycin is bactericidal. TRUE

85
Program Learning Answers

• An order is written to use high-dose vancomycin
  given via oral route to treat a MRSA cellulitis.
  Is this appropriate?
• Vancomycin given PO is only effective against C.
  difficile and is localized almost exclusively to
  the GI tract. Conversely, IV vancomycin will not
  treat C. difficile.

86
References

• Chambers, H. Chapter 21 Penicillins and ß-
  Lactam Inhibitors. Mandell, G., Bennett, J.,
  Dolin, D. Mandell, Douglas and Bennetts
  Principles and Practice of Infectious Disease.
  7th Edition. 2009.
• Andes, D., Craig, W. Chapter 22 Cephalosporins.
  Mandell, G., Bennett, J., Dolin, D. Mandell,
  Douglas and Bennetts Principles and Practice of
  Infectious Disease. 7th Edition. 2009.
• Siu, LK. et al. Correlation of in vitro
  susceptibility testing results for
  amoxicillin-clavulanate and ampicillin-sulbactam
  using a panel of beta-lactamase producing
  Enterobacteriaceae. APMIS. 1998 Sep
  106(9)917-20.
• Kacmaz, B., Sultan, N. In vitro susceptibilities
  of Escherichia coli and Klebsiella spp. to
  ampicillin-sulbactam and amoxicillin-clavulanic
  acid. Jpn J Infect Dis. 2007 Jul60(4)227-9.
• Piperacillin. Drug Monograph. In Klasco RK (Ed)
  DRUGDEX System (electronic version). Thomson
  Micromedex, Greenwood Village, Colorado, USA.
  Available at http//www.thomsonhc.com
  (cited10/12/2009).
• Piperacillin/tazobactam (Zosyn). Drug Monograph.
  In Klasco RK (Ed) DRUGDEX System (electronic
  version). Thomson Micromedex, Greenwood Village,
  Colorado, USA. Available at http//www.thomsonhc.
  com (cited10/12/2009).
• This concludes Module 2 Antibiotic Review.
• Please proceed to Module 3.

87
References

• Ticarcillin/clavulanic acid (Timentin). Drug
  Monograph. In Klasco RK (Ed) DRUGDEX System
  (electronic version). Thomson Micromedex,
  Greenwood Village, Colorado, USA. Available at
  http//www.thomsonhc.com (cited10/12/2009).
• Aztreonam. Drug Monograph. In Klasco RK (Ed)
  DRUGDEX System (electronic version). Thomson
  Micromedex, Greenwood Village, Colorado, USA.
  Available at http//www.thomsonhc.com
  (cited10/12/2009).
• Reichardt, P. et al. Leukocytopenia,
  thrombocytopenia and fever related to
  piperacillin/tazobactam treatmenta retrospective
  analysis in 38 children with cystic fibrosis.
  Infection. 1999 Nov-Dec27(6)355-6.
• Kaiser Regional Antibiogram, Northern
  California. 2009
• American Thoracic Society Infectious Disease
  Society of America. Guidelines for the management
  of adults with hosptial-acquired,
  ventilator-associated and healthcare-associated
  pneumonia. Am J Respir Crit Care Med. Vol 171. pp
  388-416, 2005.
• Chambers, H. Chapter 23 Carbapenems and
  monobactams. Mandell, G., Bennett, J., Dolin, D.
  Mandell, Douglas and Bennetts Principles and
  Practice of Infectious Disease. 7th Edition.
  2009.
• This concludes Module 2 Antibiotic Review.
• Please proceed to Module

88
References

• Paterson, D., Depestel D. Doripenem. Clin Infect
  Dis. 2009 Jul 1549(2)291-8.
• Spriet, I. Interaction between valproate and
  meropenem a retrospective study. Ann
  Pharmacother. 2007 Jul41(7)1130-6.
• ASHP Drug Product Shortages Management Resource
  Center. www.ashp.org/drugshortages/current. Last
  accessed 10/12/2009.
• Ramphal, R., Ambrose, P. Extended-spectrum
  beta-lactamases and clinical outcomes current
  data. Clin Infect Dis. 2006 Apr 1542 Suppl
  4S164-72.
• Long, R. et al. Empirical treatment of
  community-acquired pneumonia and the development
  of fluoroquinolone-resistant tuberculosis. Clin
  Infect Dis. 2009 481354-60.
• Moxfloxacin. Drug Monograph. In Klasco RK (Ed)
  DRUGDEX System (electronic version). Thomson
  Micromedex, Greenwood Village, Colorado, USA.
  Available at http//www.thomsonhc.com
  (cited10/12/2009).
• Clindamycin. Drug Monograph. In Klasco RK (Ed)
  DRUGDEX System (electronic version). Thomson
  Micromedex, Greenwood Village, Colorado, USA.
  Available at http//www.thomsonhc.com
  (cited10/12/2009).
• This concludes Module 2 Antibiotic Review.
• Please proceed to Module

89
References

• Rybak, M. et al. Therapeutic monitoring of
  vancomycin in adult patients A consensus review
  of the American Society of Health-System
  pharmacists, the Infectious Diseases Society of
  America and the Society of Infectious Diseases
  Pharmacists. Am J Health-System Pharm.
  20096682-98.
• Donskey, et al. Effect of antibiotic therapy on
  the density of vancomycin-resistant enterococci
  in the stool of colonized patients.NEJM. 2000 Dec
  28343(26)1925-32.
• Murray, B., Esteban, N. Chapter 31
  Glycopeptides (Vancomycin and teicolanin),
  Streptogramins (Quinupristin-dalfoprsitin), and
  lipopeptides (daptomycin). Mandell, G., Bennett,
  J., Dolin, D. Mandell, Douglas and Bennetts
  Principles and Practice of Infectious Disease.
  7th Edition. 2009.
• Hooper, D., Strahilevitz, J. Chapter 35
  Quinolones. Mandell, G., Bennett, J., Dolin, D.
  Mandell, Douglas and Bennetts Principles and
  Practice of Infectious Disease. 7th Edition.
  2009.
• Metronidazole. Drug Monograph. In Klasco RK
  (Ed) DRUGDEX System (electronic version).
  Thomson Micromedex, Greenwood Village, Colorado,
  USA. Available at http//www.thomsonhc.com
  (cited10/12/2009).
• Gerding, D. et al. Treatment of Clostridium
  difficie infection. Clin Infect Dis. 2008 Jan
  1546 Suppl1S32-42.

90
.

• This concludes Module 2 Antibiotic
  Review.
• Please proceed to Module 3 Allergy Review.