Module 2 (of 3): Antibiotic Review* Review of selected antimicrobials By Keith Teelucksingh, PharmD Infectious Disease Pharmacist, Kaiser Permanente Vallejo

Module 2 (of 3): Antibiotic Review*

Review of selected antimicrobialsBy Keith Teelucksingh, PharmD

Infectious Disease Pharmacist, Kaiser Permanente Vallejo With contributions by Linh Van, PharmD

Infectious Disease Pharmacist, Kaiser Permanente Oakland

See Notes

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.

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

1. Elaborate on the spectrum activity for the β-lactam-related antibiotics, aztreonam, vancomycin, clindamycin, metronidazole and the fluoroquinolones

2. Discuss the appropriate clinical uses of the broad spectrum β-lactam-related antibiotics and vancomycin

Objectives

Objectives

3. Describe the appropriate use of the anti-anaerobic agents clindamycin and metronidazole when combined with other anaerobically active antibiotics

4. Describe the appropriate use of β-lactam agents and vancomycin agents for the treatment of certain bacteria

Antibiotics to be Covered

β-Lactams Penicillins Cephalosporin

s Carbapenems

Monobactams Aztreonam

Quinolones Moxifloxacin Ciprofloxacin

Other Clindamycin Metronidazole Vancomycin

Adapted from Brett Heintz, PharmD, BCPS

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

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

Penicillins

Penicillin G Side effects

Allergic reactions (rash, blood dyscrasias, anaphylaxis) -> discussed in more detail in Module 3

Interstitial nephritis Hyperkalemia Phlebitis

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

Penicillins

Nafcillin When interpreting susceptibilities:

oxacillin = nafcillin Susceptibility to nafcillin predicts

susceptibility to cefazolin/cephalexin

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

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

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

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

Penicillins

Ampicillin/amoxicillin Side effects (in general, similar to

penicillin) Allergic reactions

Rash Eosinophilia

Leukopenia

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

See NotesNF = non formulary

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

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)

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


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


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

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


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


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

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

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

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

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

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

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

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

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*

1. What is the drug of choice for ampicillin-sensitive Enterococcus? Besides the drug of choice, what other beta-lactam(s) would work?

2. Which penicillins cover MRSA?3. What are the penicillins that would cover

MSSA?

*Program Learning Answers*

1. 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.


2. Which penicillins cover MRSA? None. No β-lactam agent covers MRSA.

3. 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.


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?


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

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

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

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

Cephalosporins

1st generation Uses

Cefazolin Cellulitis, MSSA infections, surgical

prophylaxis Cephalexin, cefadroxil

UTI, skin/soft tissue infections due to MSSA or Strep spp.

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

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

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

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

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

Cephalosporins

Side effects Similar to penicillins

Allergic reactions Blood dyscrasias

Rare

*Program Learning*

1. Which cephalosporins do not need renal adjustment?

2. How is ceftriaxone dosed for these disease states?

Community-acquired pneumonia, endocarditis, osteomyelitis, meningitis

3. Which cephalosporins have anaerobic coverage?

4. Which cephalosporins cover Pseudomonas?


1. Which cephalosporins do not need renal adjustment? Ceftriaxone only. All other cephalospsorins need to be adjusted for renal dysfunction.

2. How is ceftriaxone dosed for these disease states? CAP: 1g iv q24h, Endocarditis/Osteomyelitis: 2g iv q24h, Meningitis: 2g iv q12h


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

4. Which cephalosporins cover Pseudomonas? Ceftazidime and cefepime.

Fluoroquinolones

These are potent antibiotics that have excellent oral bioavailability

Ciprofloxacin Moxifloxacin LevofloxacinNF

Trovafloxacin (off market - hepatotoxic) Gatifloxacin (off market - dysglycemias)

NF = non-formulary

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

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

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)

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

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

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

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

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 Learning*

1. 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?

2. 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?


1. 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.


2. 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

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

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

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

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

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

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)

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 *

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 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 Learning*

1. What is the spectrum of activity for clindamycin?

2. A patient with Serratia bacteremia is started on clindamycin. What is wrong with this?

3. A patient with hospital-acquired pneumonia, on Zosyn®, is started on metronidazole. Under what circumstance would this be appropriate?


1. What is the spectrum of activity for clindamycin? Anaerobic bacteria, check sensitivities before using for either Staphylococci and Streptococci.

2. A patient with Serratia bacteremia is started on clindamycin. What is wrong with this? Clindamycin has no appreciable Gm – activity.


3. 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

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).

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.

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.

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.

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.

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.

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 Learning*

1. Patient with MSSA leg infection on vancomycin IV. Patient has no allergies. Is there a better antibiotic?

2. True/false. Vancomycin is bactericidal.3. An order is written to use high-dose PO

vancomycin to treat a MRSA cellulitis. Is this appropriate?


1. 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.

2. True/False. Vancomycin is bactericidal. TRUE


3. 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

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.

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. 2009American 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

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

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.

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This concludes Module 2: Antibiotic Review.

Please proceed to Module 3: Allergy Review.

Documents

Module 2 (of 3): Antibiotic Review* Review of selected antimicrobials By Keith Teelucksingh, PharmD Infectious Disease Pharmacist, Kaiser Permanente Vallejo