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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. Goals.

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module 2 of 3 antibiotic review
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

goals
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.

objectives
Objectives

Upon completion of this module, the participant will be able to:

  • Elaborate on the spectrum activity for the β-lactam-related antibiotics, aztreonam, vancomycin, clindamycin, metronidazole and the fluoroquinolones
  • Discuss the appropriate clinical uses of the broad spectrum β-lactam-related antibiotics and vancomycin
objectives1
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 β-lactam agents and vancomycin agents for the treatment of certain bacteria
antibiotics to be covered
Antibiotics to be Covered
  • Other
    • Clindamycin
    • Metronidazole
    • Vancomycin
  • β-Lactams
    • Penicillins
    • Cephalosporins
    • Carbapenems
  • Monobactams
    • Aztreonam
  • Quinolones
    • Moxifloxacin
    • Ciprofloxacin
lactams
β-Lactams
  • Natural penicillins: penicillin
  • Penicillinase-resistant penicillins: nafcillin, dicloxacillin
  • Aminopenicillins: ampicillin, amoxicillin
  • Extended spectrum penicillins: pipercillin, ticarcillin
  • β-lactam/β-lactamase inhibitor combinations:

Zosyn®, Unasyn®, Augmentin®, Timentin®

penicillins
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
penicillins1
Penicillins

Penicillin G

  • Side effects
    • Allergic reactions (rash, blood dyscrasias, anaphylaxis) -> discussed in more detail in Module 3
    • Interstitial nephritis
    • Hyperkalemia
    • Phlebitis
penicillins2
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

penicillins3
Penicillins

Nafcillin

  • When interpreting susceptibilities:
    • oxacillin = nafcillin
  • Susceptibility to nafcillin predicts susceptibility to cefazolin/cephalexin
penicillins4
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
penicillins5
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
penicillins6
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
penicillins7
Penicillins

Pharmacokinetic considerations

  • Bioavailability (oral)
    • Amoxicillin, Dicloxacillin > Ampicillin> PCN VK
  • High concentration in urine
  • All need to be adjusted in renal dysfunction
    • Exceptions: nafcillin, dicloxacillin
penicillins8
Penicillins

Ampicillin/amoxicillin

  • Side effects (in general, similar to penicillin)
    • Allergic reactions
      • Rash
      • Eosinophilia
    • Leukopenia
extended spectrum penicillins
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

l li combinations
βL/βLi* combinations

Unasyn® (ampicillin/sulbactam)

Augmentin® (amoxicillin/clavulanic acid)

Zosyn® (piperacillin/tazobactam)

Timentin® (ticarcillin/clavulanic acid) NF

*βL/βLi = β-lactam/β-lactamaseinhibitor

NF = non-formulary

l li combinations1
βL/βLi 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 βLi adds activity against:
    • Bacteroidies (anaerobes), β-lactamase producing Gm – (E. coli, Klebsiella, Serratia) & Gm + (Enterococci, MSSA)
l li combinations2
βL/βLi 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

l li combinations3
βL/βLi 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
l li combinations4
βL/βLi 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
l li combinations5
βL/βLi 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

l li combinations6
βL/βLi 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

l li combinations7
βL/βLi 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
carbapenems
Carbapenems
  • The most potent antibiotic in theβ-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

carbapenems1
Carbapenems *
  • Spectrum of activity
    • Broadest coverage including Gm+, Gm- (especially drug resistant species -> 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

carbapenems2
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

carbapenems3
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

carbapenems4
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

carbapenems5
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
carbapenems6
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.
monobactams
Monobactams

Aztreonam (only drug in class, Azactam®):

  • Monocylic β-lactam ring (traditional β-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

program learning
*Program Learning*
  • What is the drug of choice for ampicillin-sensitive 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?
program learning answers
*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.

program learning answers1
*Program Learning Answers*

Which penicillins cover MRSA? None. No β-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.

program learning answers2
*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?
program learning answers3
*Program Learning Answers*

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

cephalosporins
Cephalosporins
  • These compounds are structurally related to the penicillins due to presence of β-lactam ring. This will only focus on cephalosporins used commonly in the inpatient setting
  • 1st generation
  • 2nd generation
  • 3rd generation
  • 4th generation
cephalosporins1
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
cephalosporins2
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
cephalosporins3
Cephalosporins

1st generation

  • Uses
    • Cefazolin
      • Cellulitis, MSSA infections, surgical prophylaxis
    • Cephalexin, cefadroxil
      • UTI, skin/soft tissue infections due to MSSA or Strep spp.
cephalosporins4
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
cephalosporins5
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
cephalosporins6
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
cephalosporins7
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
cephalosporins8
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

cephalosporins9
Cephalosporins
  • Side effects
    • Similar to penicillins
      • Allergic reactions
    • Blood dyscrasias
      • Rare
program learning1
*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?
program learning answers4
*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/Osteomyelitis: 2g iv q24h, Meningitis: 2g iv q12h
program learning answers5
*Program Learning Answers*

Which cephalosporins have anaerobic coverage? Cefoxitin and cefotetan; both are 2nd generation cephalosporins.

Which cephalosporins cover Pseudomonas? Ceftazidime and cefepime.

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

NF = non-formulary

fluoroquinolones1
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

fluoroquinolones2
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
fluoroquinolones3
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)
fluoroquinolones4
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

fluoroquinolones5
Fluoroquinolones
  • Moxifloxacin
    • Coverage:
      • Most active fluoroquinolone for S. pneumoniae
      • Excellent anaerobic coverage ->B. 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
fluoroquinolones6
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
fluoroquinolones7
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
fluoroquinolones8
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
program learning2
*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?
program learning answers6
*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.
program learning answers7
*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.

clindamycin
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
clindamycin1
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
clindamycin2
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
metronidazole
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
metronidazole1
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
metronidazole2
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)
metronidazole3
Metronidazole
  • Drug interactions
    • Warfarin
      • Increased INRs, consider using PO vancomycin
    • Lithium
    • EtOH
      • Disulfiram-like reaction with EtOH
  • Side effects
    • Metallic taste, dark urine
double anaerobic coverage
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, βL/βLi combos, moxifloxacin, tigecycline

See Notes

double anaerobic coverage1
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
program learning3
*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?

program learning answers8
*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.
program learning answers9
*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.

vancomycin
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).
vancomycin1
Vancomycin
  • Delayed killing against S. aureus and MRSA  especially with high inoculum size (in vitro).

**If S. aureus isolate is β-lactam sensitive (i.e MSSA), use β-lactam antibiotic  better killing, better outcomes.

vancomycin2
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.
vancomycin3
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.

vancomycin4
Vancomycin
  • Side effects
    • Nephrotoxicity with other nephrotoxic drugs.
    • Redman’s 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.
vancomycin5
Vancomycin
  • Clinical uses
    • Serious infections where MRSA is suspected.
    • Therapy for Gm + infections in patients with serious allergic reactions to β-lactam antibiotics.
    • Treatment for C. difficile colitis (given PO).
      • Systemic infections cannot be treated with vancomycin PO  localized to gut.
vancomycin6
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
program learning4
*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?
program learning answers10
*Program Learning Answers*
  • Patient with MSSA leg infection on vancomycin IV. Patient has no allergies. Is there a better antibiotic? Yes. The β-lactams have better killing activity vs. MSSA than vancomycin. Nafcillin, dicloxacillin and cephalexin are potential options.
  • True/False. Vancomycin is bactericidal. TRUE
program learning answers11
*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.

references
References
  • Chambers, H. Chapter 21: Penicillins and β- Lactam Inhibitors. Mandell, G., Bennett, J., Dolin, D. Mandell, Douglas and Bennett’s 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 Bennett’s 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 Jul;60(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 (cited:10/12/2009).
  • 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 (cited:10/12/2009).

This concludes Module 2: Antibiotic Review.

Please proceed to Module 3.

references1
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 (cited:10/12/2009).
  • Aztreonam. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com (cited:10/12/2009).
  • Reichardt, P. et al. Leukocytopenia, thrombocytopenia and fever related to piperacillin/tazobactam treatment—a retrospective analysis in 38 children with cystic fibrosis. Infection. 1999 Nov-Dec;27(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 Bennett’s Principles and Practice of Infectious Disease. 7th Edition. 2009.

This concludes Module 2: Antibiotic Review.

Please proceed to Module

references2
References
  • Paterson, D., Depestel D. Doripenem. Clin Infect Dis. 2009 Jul 15;49(2):291-8.
  • Spriet, I. Interaction between valproate and meropenem: a retrospective study. Ann Pharmacother. 2007 Jul;41(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 15;42 Suppl 4:S164-72.
  • Long, R. et al. Empirical treatment of community-acquired pneumonia and the development of fluoroquinolone-resistant tuberculosis. Clin Infect Dis. 2009; 48:1354-60.
  • Moxfloxacin. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com (cited:10/12/2009).
  • Clindamycin. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com (cited:10/12/2009).

This concludes Module 2: Antibiotic Review.

Please proceed to Module

references3
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. 2009;66:82-98.
  • Donskey, et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients.NEJM. 2000 Dec 28;343(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 Bennett’s 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 Bennett’s 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 (cited:10/12/2009).
  • Gerding, D. et al. Treatment of Clostridium difficie infection. Clin Infect Dis. 2008 Jan 15;46 Suppl1:S32-42.
slide90
.

This concludes Module 2: Antibiotic Review.

Please proceed to Module 3: Allergy Review.