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Cephalosporins

All Cephalosporins

Bactericidal

Bind to Penicillin Binding Proteins

Resistant to Penicillinase, but not other classes of β-lactamases (e.g. Extendend Spectrum Beta-Lacatamases
or ESBLs)

Renal excretion

Side Effects

● Hypersensitivity reactions (Cross-hypersensitivity with penicillins 1-3%)

● Superinfections: Enterococci, Enterobacter and Candida

THE CEPHALOSPORIN FAMILY

THE CEPHALOSPORINS
CATEGORY PARENTERAL AGENTS ORAL AGENTS
First Generation Cefazolin Cephalexin
Second Generation Cefotetan, Cefoxitin, Cefuroxime Cefuroxime axetil, Cefaclor
Third Generation Cefotaxime, Ceftazidime, Ceftriaxone Cefixime, Cefdinir
Fourth Generation Cefepime
Fifth Generation Ceftaroline

Generational Coverage

Generation Gram Negatives Gram Positives β-Lactamase Stability

1st + +++ +/-
2nd ++ ++ +
3rd +++ + ++
4th +++ ++ +++
5th +++ +++ ++++

Note: There are generational shifts from gram-positive to gram-negative coverage &
resistance to β-lactamases.

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1st Generation - Narrow Spectrum

1st Gen Cephalosporin Coverage & Indications

● Cefazolin - iv
● Cephalexin - po

Spectrum

● Gram Positive Cocci, including MSSA (Does NOT cover Enterococcus)

● Gram Negative Rods
● No CNS penetration

Coverage

● MSSA
● Streptococci Grp A,B,C,G
● Strep viridans
● S. pneumoniae
● H. influenzae
● E. coli
● Klebsiella pneumoniae
● Proteus mirabilis

Common Uses

● Skin & Soft Tissue Infections (SSTI)

● Upper Respiratory Tract Infections
● Surgical Prophylaxis

Keywords

Cephalexin

● Trade Names: generic, Keflex ®

● Drug Class: Cephalosporin 1st generation (oral)
● Mechanism of Action:
❍ Similar to penicillins. Cephalosporins are generally resistant to penicillinase.
● Indications:
❍ See 1st Gen Coverage & Uses
● Side Effects:

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❍hypersensitivity
● Pharmacokinetics:
❍orally effective, renal clearance.
● References:
❍Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍rxlist.com (Keflex ®)

Keywords

Cefazolin

● Trade Names: generic, Kefzol, Ancef ®

● Drug Class: Cephalosporin 1st generation (parenteral: iv or im)
● Indications:
❍ Same spectrum of activity as cephalexin
❍ See 1st Gen Coverage & Uses
● Pharmacokinetics:
❍ parenteral administration (injection) only; elimination via the kidney.
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Cefazolin ®)

Keywords

2nd Generation - Intermediate Spectrum

2nd Gen Cephalosporin Coverage & Indications

● Cefuroxime - iv or po
● Cefaclor - po
● Cefoxitin - iv
● Cefotetan - iv (MMT)
❍MMT = methyl-thio-tetrazole (can cause disuliram-like reaction)

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Half life = 1hr (except Cefotetan = 4 hrs)

Coverage

Same as 1st Generation Plus:

● β-lactamase positive H. influenzae

● Moraxella catarrhalis
● Neisseria meningitidis
● E. coli
● Klebsiella pneumoniae
● Proteus
● Oral anaerobes
● Cefoxitin & Cefotetan cover B. fragilis

Holes in Coverage

● No CNS Penetration
● Cefuroxime does not have good coverage of gut anaerobes

Common Uses

● Community Acquired Pneumonia

● Bronchitis, Sinusitis, Otitis
● Skin & Soft Tissue Infections (SSTI)
● MSSA
● Abdominal Surgical Prophylaxis

● Cefoxitin or Cefotetan can be used as monotherapy of mild intra-abdominal & pelvic

infections
❍ Coverage includes many gut anaerobes (e.g. B. fragilis)
● Cefuroxime
❍ Covers pneumococcus & H. influenzae
❍ Community Acquired Pneumonia, Sinusitis & Otitis
❍ Does NOT cover gut anaerobes

● Reference:
❍Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.

Keywords

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Cefaclor

● Trade Names: generic, Ceclor ®

● Drug Class: Cephalosporin 2nd generation (oral)
● Indications:
❍ See 2nd Gen Coverage & Uses
● Pharmacokinetics:
❍ oral absorption, renal clearance
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Ceclor ®)

Keywords

Cefotetan

● Trade Names: generic

● Drug Class: Cephalosporin 2nd generation (parenteral)
● Indications:
❍ See 2nd Gen Coverage & Uses
● Pharmacokinetics:
❍ parenteral absorption, renal clearance
● Major drug interactions:
❍ The methylthiotetrazole ring of some cephalosporins (cefamandole, cefotetan, cefmetazole, and
cefoperazone) may cause severe disulfiram-like reactions; so alcohol and medications containing
alcohol should be avoided.
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Cefotetan)

Clinical Pharmacology. 13e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange. *
[[https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-
drugs/cephalosporins == Keywords ==

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Cefoxitin

● Trade Names: Mefoxin ®

● Drug Class: Cephalosporin 2nd generation (parenteral)
● Mechanism of Action:
❍ Similar to penicillin
❍ Increased activity against Gram negative bacilli and greater stability against beta-lactamase
inactivation
● Indications:
❍ See 2nd Gen Coverage & Uses
● Pharmacokinetics:
❍ parenteral, injection, renal clearance
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Mefoxin ®)

Keywords

Cefuroxime

● Trade Name: Cefuroxime, Cefuroxime axetil (Ceftin ®)

● Drug Class: Cephalosporin 2nd generation (oral or parenteral)
● Indications:
❍ Axetil ester form used for oral administration.
❍ See 2nd Gen Coverage & Uses
● Pharmacokinetics:
❍ oral or parenteral forms
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Cefuroxime)
❍ rxlist.com: (Cefuroxime axetil; Ceftin ®)

Keywords

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3rd Generation - Broad Spectrum

3rd Gen Cephalosporin Coverage & Indications

● 3rd Generation:
❍Cefotaxime - iv
❍Ceftazidime - iv
❍Ceftriaxone - iv
❍Cefixime - po
❍Cefdinir - po

● Half life = 2hrs (except Ceftriaxone = 8 hrs)

● Ceftriaxone must NOT be administered with calcium containing solutions. Potentially fatal
calcium precipitates can form in the lungs & kidney.

3rd Generation Coverage

Same as 1st Generation Plus:

● Expanded gram-negative coverage

● Oral anaerobes
● S. aureus (OSSA)
● Strep pneumoniae
● Strep Grp A,B,C,G
● Strep viridans
● Gram negative rods
● N. gonorrhea
● All cover B. fragilis EXCEPT cefotaxime & ceftazidime
● P. aeruginosa - ceftazidine only

Holes in 3rd Generation Coverage

● Poor gram-positive coverage

● E. faecium
● MRSA
● All cover OSSA EXCEPT ceftazidime
● Legionella / atypicals
● Listeria
● Acinetobacter
● Not all cover Pseudomonas

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3rd Generation Common Uses

● Community acquired pneumonia

● Bacterial MENINGITIS (except Listeria) (3rd & 4th Gen cross the BBB to enter the CSF)
● UTIs (3rd & 4th Gen penetrate into tissues reasonably well)
● Anogenital gonorrhea: ceftriaxone or cefixime
● Lyme disease
● Viridans strep endocarditis
● Intra-Abdominal & Pelvic Infections: ceftriaxone + metronidazole or clindamycin
● Hospital Acquired Pneumonia: ceftazidime only

Reference:

● Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors).
McGraw-Hill / Lange.

Keywords

Cefotaxime

● Trade Name: Claforan ®

● Drug Class: Cephalosporin 3rd generation (parenteral)
● Indications:
❍ See 3rd Generation Coverage & Uses
● Pharmacokinetics:
❍ parenteral administration
❍ renal clearance
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Claforan ®)

Keywords

Ceftriaxone

● Trade Name: Rocephin ®

● Drug Class: Cephalosporin 3rd generation (parenteral)

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● Indications:
❍ A drug of choice for treatment of bacterial meningitis
❍ Treatment of Pyelonephritis (UTIs)
❍ Uncomplicated gonorrhea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae
❍ See 3rd Generation Coverage & Uses
● Pharmacokinetics:
❍ Longer half-life (7-8 hr), parenteral administration
❍ excreted via the bile tract, no dosage adjustment required in renal insufficiency
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2015): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 13th Ed Katzung BG, Trevor AJ (Editors).
McGraw-Hill / Lange.
❍ rxlist.com (Rocephin ®)

Keywords

Cefixime

● Trade Names: Suprax ®

● Drug Class: Cephalosporin 3rd generation (oral)
● Indications:
❍ See 3rd Generation Coverage & Uses
● Pharmacokinetics:
❍ oral administration
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍ rxlist.com (Ceptaz ®)

Keywords

Ceftazidime

● Trade Names: generic, Fortaz, Tazdime, Ceptaz ®

● Drug Class: Cephalosporin 3rd generation (parenteral)
● Indications:
❍ See 3rd Generation Coverage & Uses
❍ effective against Pseudomonas aeruginosa (as does the 4th generation cefepime)
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● Pharmacokinetics:
❍parenteral administration
● References:
❍Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ
(Editors). McGraw-Hill / Lange.
❍rxlist.com (Ceptaz ®)

Keywords

4th Generation - Adds Pseudomonas

Coverage

4th Generation Coverage & Uses

● Cefepime
❍Good gram-positive & gram-negative coverage
❍Anti-Pseudomonal (including ceftazidime resistant isolates)
❍Penetrates CSF
❍Limited anaerobic coverage

Cefepime

● Trade Name: Maxipime ®

● Drug Class: Cephalosporin 4th generation (parenteral)
● Indications:
❍ Good gram-positive & gram-negative coverage
❍ Anti-Pseudomonal (including ceftazidime resistant isolates)
❍ Penetrates CSF
❍ Limited anaerobic coverage
● Pharmacokinetics:
❍ parenteral administration
❍ renal clearance
● References:
❍ Bartlett JG, Auwaerter PG, Pham PA (2010): The Johns Hopkins ABX Guide. Diagnosis and
Treatment of Infectious Diseases. 2010 2nd Edition. Jones & Bartlett Publishers, Sudbury MA.
(ISBN: 978-0-7637-8108-8)
❍ Deck DH, Winston LG (2012): Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics
(Chapter 43). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ

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(Editors). McGraw-Hill / Lange.

❍ rxlist.com (Maxipime ®)

Keywords

5th Generation - Very Broad Spectrum

Ceftaroline

Fifth Generation Cephalosporin

● Ceftaroline fosamil is newly FDA approved prodrug formulation of ceftaroline

● Effective against gram-positive bacteria, and retains the activity of later-generation cephalosporins
with broad-spectrum activity against gram-negative bacteria
● it has increased affinity for PBP2a that mediates methicillin resistance in Staphylococci
● indicated for treating:
❍ ORSA
❍ skin & soft tissue infections
❍ community-acquired pneumonia

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