Professional Drug Information > Kefzol

Cephalosporins (Systemic)

This monograph includes information on the following:


Note: Products containing cefixime were withdrawn from the U.S. market by Wyeth in October 2002^{179}

1) Cefaclor
2) Cefadroxil
3) Cefamandole
4) Cefazolin
5) Cefdinir ^†
6) Cefditoren ^†
7) Cefepime
8) Cefixime ^*
9) Cefonicid ^†
10) Cefoperazone ^†
11) Cefotaxime
12) Cefotetan
13) Cefoxitin
14) Cefpodoxime ^†
15) Cefprozil
16) Ceftazidime
17) Ceftibuten ^†
18) Ceftizoxime
19) Ceftriaxone
20) Cefuroxime
21) Cephalexin
22) Cephalothin ^*
23) Cephapirin ^†
24) Cephradine ^†

VA CLASSIFICATION
Cefaclor
Primary: AM116

Cefadroxil
Primary: AM115

Cefamandole
Primary: AM116

Cefazolin
Primary: AM115

Cefdinir
Primary: AM117

Cefditoren
Primary: AM117

Cefepime
Primary: AM118

Cefixime
Primary: AM117

Cefonicid
Primary: AM116

Cefoperazone
Primary: AM117

Cefotaxime
Primary: AM117

Cefotetan
Primary: AM116

Cefoxitin
Primary: AM116

Cefpodoxime
Primary: AM117

Cefprozil
Primary: AM116

Ceftazidime
Primary: AM117

Ceftibuten
Primary: AM117

Ceftizoxime
Primary: AM117

Ceftriaxone
Primary: AM117

Cefuroxime
Primary: AM116

Cephalexin
Primary: AM115

Cephalothin
Primary: AM115

Cephapirin
Primary: AM115

Cephradine
Primary: AM115


Commonly used brand name(s): Ancef⁴; Apo-Cefaclor¹; Apo-Cephalex²¹; Ceclor¹; Ceclor CD¹; Cedax¹⁷; Cefadyl²³; Cefizox¹⁸; Cefobid¹⁰; Cefotan¹²; Ceftin²⁰; Cefzil¹⁵; Ceporacin²²; Ceptaz¹⁶; Claforan¹¹; Duricef²; Fortaz¹⁶; Keflex²¹; Keflin²²; Keftab²¹; Kefurox²⁰; Kefzol⁴; Mandol³; Maxipime⁷; Mefoxin¹³; Monocid⁹; Novo-Lexin²¹; Nu-Cephalex²¹; Omnicef⁵; PMS-Cephalexin²¹; Rocephin¹⁹; Spectracef ™⁶; Suprax⁸; Tazicef¹⁶; Tazidime¹⁶; Vantin¹⁴; Velosef²⁴; Zinacef²⁰.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

^†Not commercially available in Canada.

Category:


Antibacterial (systemic)—

Indications

Note: Products containing cefixime were withdrawn from the U.S. market by Wyeth in October 2002^{179}

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

General considerations
Cephalosporins have been classified by “generation” based on their spectrum of antibacterial activity, providing a useful, although somewhat arbitrary, means of grouping the many cephalosporins available. Several of the newer cephalosporins with an expanded spectrum of activity do not fit into any one generation but overlap into others. These medications have been placed into the generation that most closely describes their antibacterial spectrum.

First-generation cephalosporins include cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, and cephradine.

Second-generation cephalosporins include cefaclor, cefamandole, cefonicid, cefotetan, cefoxitin, cefprozil, and cefuroxime.

Third-generation cephalosporins include cefdinir, cefditoren, cefixime, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone.

The fourth-generation cephalosporin is cefepime.

Selection of any antimicrobial agent usually is based on the organism(s) that is present or most likely to be present, site(s) of infection, resistance patterns, and the side effects, cost, and pharmacokinetic properties of the cephalosporin. (See also Table 1 and Table 2 .)

First-generation cephalosporins have the highest degree of activity compared with other cephalosporins against most gram-positive bacteria, including beta-lactamase–producing Staphylococcus aureus and most streptococci; exceptions include methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae . No cephalosporin is effective against Enterococcus faecalis , Enterococcus faecium , or Listeria monocytogenes infections ^{{112} {133} {145}}. Gram-negative bacteria coverage is generally limited to Escherichia coli , Klebsiella pneumoniae , and Proteus mirabilis ^{{133} {146}}; cephalothin, cephapirin, and cephradine are also active, although poorly, against Haemophilus influenzae ^{{29} {30} {60} {145}}. Cephalothin and cefazolin have similar spectra of activity in vitro . Although cefazolin is more active against E. coli and Klebsiella species, it is more susceptible to staphylococcal penicillinases than is cephalothin ^{{101} {112}}. Cephalexin, cefadroxil, and cephradine all have very similar activities in vitro and are available only in an oral dosage form ^{{03} {27} {30}}.

First-generation cephalosporins are used to treat bacterial endocarditis, bone and joint infections, otitis media, pneumonia, septicemia, skin and soft tissue infections, including burn wound infections, and urinary tract infections caused by susceptible bacterial organisms ^{{03} {05} {27} {29} {30} {60}}. They are not effective in treating meningitis. These medications are possible alternatives to the penicillins for staphylococcal and nonenterococcal streptococcal infections, including pneumonias, bone and joint infections, and bacterial endocarditis ^{112}. Cefazolin is the preferred agent for use in perioperative prophylaxis because of its longer half-life ^{112}. Because first-generation cephalosporins provide inconsistent coverage against gram-negative bacilli, their empiric use as therapy for nosocomial infections is not recommended ^{112}.

Second-generation cephalosporins have enhanced activity, compared with the first-generation cephalosporins, against E. coli , Klebsiella species, and P. mirabilis ; in addition, they have greater activity in vitro against a larger number of gram-negative bacteria, including H. influenzae , indole-positive Proteus , Moraxella (Branhamella) catarrhalis , Neisseria meningitidis , Neisseria gonorrhoeae , and some strains of Serratia and Enterobacter species ^{{01} {04} {09} {12} {13} {15} {24}}. Serratia and Enterobacter species may induce beta-lactamases that inactivate the drug after a period of exposure to the cephalosporin, producing a resistance that may be expressed late; this resistance may not be detectable by disc sensitivity techniques ^{{105} {106}}. The second-generation cephalosporins have slightly less or variable activity against most gram-positive cocci, and none have activity against Acinetobacter species or Pseudomonas aeruginosa ^{133}.

Cefaclor and cephalexin have comparable activity in vitro against most gram-positive cocci ^{{01} {27}}; however, cefaclor has better activity than cephalexin against H. influenzae , E. coli , M. catarrhalis , and P. mirabilis ^{112}. Cefamandole, cefonicid, and cefuroxime all have similar activities in vitro ^{101}. However, cefuroxime may be more stable against plasmid-encoded beta-lactamases (e.g., TEM-1) than is cefamandole ^{103}, and cefonicid has less activity in vitro against S. aureus ^{104}. Cefuroxime sodium is the only second-generation cephalosporin to penetrate into the cerebrospinal fluid (CSF) ^{{25} {133}}. Cefprozil has in vitro activity that covers a broad range of organisms, including many gram-positive and gram-negative organisms that are typically covered by first-generation cephalosporins. It also has good activity against H. influenzae , M. catarrhalis , Citrobacter diversus , penicillinase-producing strains of N. gonorrhoeae , and P. mirabilis ^{{15} {101}}.

Second-generation cephalosporins are used in the treatment of bone and joint infections, pneumonia, septicemia, skin and soft tissue infections, including burn wound infections, and urinary tract infections caused by susceptible bacterial organisms ^{{01} {04} {09} {12} {13} {15} {24} {25}}. Cefuroxime has been used to treat meningitis caused by S. pneumoniae , H. influenzae (including ampicillin-resistant strains), and N. meningitidis , although third-generation cephalosporins have better penetration into the CSF ^{{101} {133}}. Also, delayed sterilization of the CSF has been reported in children being treated with cefuroxime for bacterial meningitis ^{{25} {47}}. Because cefaclor has good activity against many strains of H. influenzae , it is used in the treatment of amoxicillin-resistant otitis media and sinusitis ^{133}. This is also true of cefuroxime axetil, an oral prodrug that is hydrolyzed to cefuroxime after absorption. It has been used to treat mild to moderate bronchitis, Lyme disease, otitis media, pharyngitis and tonsillitis, sinusitis, skin and soft tissue infections, uncomplicated gonococcal urethritis, and urinary tract infections ^{{24} {112}}. Cefprozil is also used to treat bronchitis, otitis media, pharyngitis and tonsillitis, sinusitis, and skin and soft tissue infections ^{15}.

Cefoxitin and cefotetan have the greatest activity of all the cephalosporins against anaerobes, particularly the Bacteroides fragilis group ^{112}. Cefoxitin has the greatest stability in the presence of beta-lactamases produced by the B. fragilis group ^{133}. Cefotetan has activity similar to that of cefoxitin against B. fragilis , but cefotetan has greater activity than cefoxitin against aerobic gram-negative bacilli in general ^{112}. Most strains of Bacteroides distasonis , Bacteroides ovatus , and Bacteroides thetaiotaomicron are resistant to cefotetan in vitro ^{12}. Many of the second- and third-generation cephalosporins that are active against anaerobic organisms are not effective against resistant strains of the B. fragilis group.

Cefoxitin and cefotetan are used primarily in the treatment of mixed aerobic-anaerobic bacterial infections, including aspiration pneumonia, diabetic foot infections, intraabdominal infections, and female pelvic infections ^{112}. They are also used prophylactically to help prevent perioperative infections that may result from colorectal surgery and appendectomies, and in the treatment of penicillin-resistant strains of gonorrhea ^{112}.

Most third-generation cephalosporins have a high degree of stability in the presence of beta-lactamases (penicillinases and cephalosporinases), and, therefore, have excellent activity against a wide spectrum of gram-negative bacteria, including penicillinase-producing strains of N. gonorrhoeae and most Enterobacteriaceae ( Citrobacter , E. coli , Enterobacter , Klebsiella , Morganella , Proteus , Providencia , and Serratia species) ^{{08} {10} {11} {14} {17} {20} {22} {23}}. However, third-generation cephalosporins in general are susceptible to hydrolysis by chromosomally encoded beta-lactamases ^{101}. Cefdinir has no activity against Enterobacterspecies. ^{160}Cefoperazone tends to have slightly less activity against Enterobacteriaceae than the other third-generation cephalosporins because of its greater susceptibility to plasmid-encoded beta-lactamases (e.g., TEM-1, TEM-2) ^{140}. Strains of P. aeruginosa , Serratia , and Enterobacter species may develop resistance to the cephalosporin after a period of exposure due to induction of beta-lactamases ^{{105} {106} {110}}. The third-generation cephalosporins are generally not as active against gram-positive cocci as are the first- and second-generation cephalosporins ^{101}. Cefotaxime, ceftizoxime, and ceftriaxone all have similar activity in vitro . Cefixime, one of three oral third-generation cephalosporins, has the most activity of all oral cephalosporins against Streptococcus pyogenes , S. pneumoniae , and all gram-negative bacilli, including beta-lactamase–producing strains of H. influenzae , M. catarrhalis , and N. gonorrhoeae ^{{102} {133}}. Cefixime has little activity against staphylococci.^{08}. Cefpodoxime is also an oral third-generation cephalosporin; its spectrum of activity is very similar to that of cefixime, except that cefpodoxime also has some activity against S. aureus and Staphylococcus saprophyticus ^{101}. Most species of Enterobacter , Enterococcus , Pseudomonas , Morganella , and Serratia are resistant to cefpodoxime ^{107}. Ceftibuten is the oral third-generation cephalosporin that is most resistant to beta-lactamases ^{{102} {108}}. It has a broad spectrum of activity in vitro against many gram-negative and selected gram-positive microorganisms, including H. influenzae , M. catarrhalis , S. pneumoniae , and S. pyogenes ^{{20} {102}}.

Ceftazidime has the greatest activity of the third-generation cephalosporins against P. aeruginosa ^{140}. Cefoperazone is less effective than ceftazidime, but more effective than cefotaxime, against P. aeruginosa ^{101}. The other third-generation cephalosporins tend to have variable activity against this pathogen ^{133}. Cefdinir and cefixime have no activity against Pseudomonas species. ^{08}{160}Cefoperazone achieves higher biliary concentrations than the other third-generation cephalosporins but has poor CSF penetration ^{112}.

Cefditoren has activity against Haemophilus influenzae (including β-lactamase-producing strains), Haemophilus parainfluenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), Staphylococcus aureus (including β-lactamase-producing strains), Streptococcus pneumoniae (penicillin–susceptible strains only), and Streptococcus pyogenes.^{175}

Third-generation cephalosporins and aminoglycosides (amikacin, gentamicin, netilmicin, or tobramycin) are synergistic in vitro against certain susceptible and resistant strains of P. aeruginosa as well as Serratia marcescens and other Enterobacteriaceae, including Enterobacter cloacae , E. coli , K. pneumoniae , and P. mirabilis ^{{10} {11} {17} {131}}.

Third-generation cephalosporins are used in the treatment of serious gram-negative bacterial infections, including bone and joint infections, female pelvic infections, intraabdominal infections, gram-negative pneumonia, septicemia, skin and soft tissue infections, including burn wound infections, and complicated urinary tract infections caused by susceptible organisms ^{{110} {112}}. Cefotaxime, ceftazidime, ceftizoxime, and ceftriaxone are used to treat meningitis in both children and adults ^{{11} {17} {22} {23}}. Single-dose cefixime, cefotaxime, cefpodoxime, ceftizoxime, and ceftriaxone have been found to be effective in the treatment of uncomplicated gonorrhea ^{{08} {11} {14} {22} {23}}; single-dose ceftriaxone is used to treat acute otitis media ^{23}; and cefuroxime axetil, [ceftriaxone], and [cefotaxime] are also effective in the treatment of Lyme disease ^{{24} {112} {113}}.

The fourth-generation cephalosporin cefepime generally is more resistant to hydrolysis by beta-lactamases than are the third-generation cephalosporins ^{101}. However, some medical experts group cefepime with the third-generation cephalosporins ^{147}. Cefepime is stable against plasmid-encoded beta-lactamases (e.g., TEM-1, TEM-2, SHV-1) and is also relatively resistant to the inducible chromosomally encoded beta-lactamases ^{{101} {112}}; in addition, it penetrates rapidly into gram-negative bacteria and targets multiple essential penicillin-binding proteins ^{161}. These properties of cefepime make it a useful agent in treating infections caused by many Enterobacteriaceae, including Citrobacter freundii and E. cloacae , that are resistant to other cephalosporins ^{109}. Although cefepime has similar activity to ceftazidime against P. aeruginosa and other gram-negative bacteria ^{{110} {111}}, cefepime is less active than ceftazidime against other Pseudomonas species and Stenotrophomonas (Pseudomonas) maltophilia ^{101}{161}. The activity against gram-positive microorganisms is similar for cefepime, cefotaxime, and ceftriaxone. Cefepime is inactive against , methicillin-resistant staphylococci, penicillin-resistant pneumococci, most strains of Clostridium difficile, and most strains of enterococci such as Enterococcus faecalis^{{07} {101}{161}}.

Cefepime is effective in the treatment of complicated intraabdominal infections, pneumonia, uncomplicated skin and soft tissue infections, complicated and uncomplicated urinary tract infections, and in the empiric treatment of febrile neutropenia ^{161}. [It is also used in the treatment of bronchitis and septicemia ^{64}.]

Accepted

Biliary tract infections (treatment)¹—Cefazolin ^{05} is indicated in the treatment of biliary tract infections caused by susceptible organisms.

Bone and joint infections (treatment)—[ Cefaclor]¹, [cefadroxil ]¹ , cefamandole ^{{04} {55}}, cefazolin ^{{05} {56}}, [ cefixime]¹ , cefonicid^{1 {09}}, [cefoperazone]¹ , cefotaxime^{1 {11}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, [cefpodoxime]¹ , [cefprozil]¹ , ceftazidime ^{{17} {71}}, ceftizoxime ^{{21} {72}}, ceftriaxone ^{{23} {73}}, cefuroxime ^{{25} {58}}, cephalexin ^{{27} {59}}, [cephalothin ] ^{60}, cephapirin^{1 {29}}, and [cephradine]¹ are indicated in the treatment of bone and joint infections caused by susceptible organisms.

Bronchitis (treatment)—Cefaclor ^{{02} {54}}, cefixime ^{{08} {65}}, cefprozil^{1 {15}}, and cefuroxime axetil ^{{24} {74}} are indicated in the treatment of secondary bacterial infections of acute bronchitis caused by susceptible organisms.

Bronchitis, bacterial exacerbations (treatment)— Cefaclor^{1 {02}}, cefdinir^{160}, cefditoren^{1 {175}} [cefepime] ^{64}, cefixime^{1 {08}}, cefpodoxime^{1 {14}}, cefprozil ^{1 {15}}, ceftibuten^{1 {20}}, and cefuroxime axetil^{1 {24}} are indicated in the treatment of bacterial exacerbations of chronic bronchitis caused by susceptible organisms.

Endocarditis, bacterial (treatment)—Cefazolin ^{{05} {56}}, [cephalothin] , cephapirin^{1 {29}}, and [ cephradine]¹ are indicated in the treatment of bacterial endocarditis caused by susceptible organisms.

Genitourinary tract infections (treatment)—Cefazolin ^{{05} {63}}, cefoperazone ^{1 {10}}, cefotaxime ^{11}, cephalexin ^{{27} {59}}, [ cephalothin] ^{60}, and cephradine ^{1 {30}} are indicated in the treatment of genitourinary tract infections, including epididymitis ^{05} and prostatitis ^{{05} {27} {30}}.

Gonorrhea, disseminated (treatment)¹—Cefuroxime ^{25} is indicated in the treatment of disseminated gonorrhea.

Gonorrhea, uncomplicated (treatment)—Cefixime ^{{08} {65}}, cefotaxime ^{{11} {66}}, cefpodoxime^{1 {14}}, ceftizoxime^{1 {21}}, ceftriaxone ^{{23} {73}}, cefuroxime ^{{25} {58}}, and cefuroxime axetil ^{{24} {74}} are indicated in the treatment of uncomplicated gonorrhea.

Impetigo (treatment)¹—Cefadroxil ^{03}, cefuroxime axetil ^{24}, and [cephalexin] ^{{142} {143} {144}} (Evidence rating: III) are indicated in the treatment of impetigo.

Intraabdominal infections (treatment)—Cefamandole ^{{04} {55}}, cefepime ^{{161} {64}}, cefoperazone^{1 {10}}, cefotaxime ^{{11} {66}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, ceftazidime ^{{17} {71}}, ceftizoxime ^{{21} {72}}, ceftriaxone ^{{23} {73}}, and [cephalothin] ^{60} are indicated in the treatment of intraabdominal infections caused by susceptible organisms.

Lyme disease (treatment)¹—[Cefotaxime], [ceftriaxone] , and cefuroxime axetil ^{24} are indicated in the treatment of Lyme disease.

Meningitis (treatment)—Cefotaxime ^{{11} {66}}, ceftazidime ^{{17} {71}}, ceftizoxime^{1 {21}}, ceftriaxone ^{{23} {73}}, and cefuroxime ^{{25} {58}} are indicated in the treatment of meningitis caused by susceptible organisms.
—Although indicated, cefuroxime is no longer considered a medication of choice in the treatment of bacterial meningitis due to its poor coverage of penicillin-resistant S. pneumoniae and subsequent therapeutic failures ^{148}.

Neutropenia, febrile (treatment)—Cefepime ^{{161} {64}} and [ceftazidime ]^{1 {35}} are indicated for empiric treatment of febrile neutropenia.
—In patients at high risk for severe infection, including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia, antimicrobial therapy alone may not be appropriate ^{161}.

Otitis media (treatment)—Cefaclor ^{{01} {54}}, [cefadroxil]¹ , [cefazolin]¹ , cefdinir ^{160}, cefixime ^{{08} {65}}, cefpodoxime^{1 {14}}, cefprozil ^{{15} {69}}, ceftibuten^{1 {20}}, ceftriaxone ^{1 {23}}, cefuroxime axetil ^{{24} {74}}, cephalexin ^{{27} {59}}, [cephalothin]¹ , [cephapirin]¹ , and cephradine^{1 {30}} are indicated in the treatment of otitis media caused by susceptible organisms.

Pelvic infections, female (treatment)— Cefoperazone^{1 {10}}, cefotaxime ^{{11} {66}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, cefpodoxime^{1 {14}}, ceftazidime ^{1 {17}}, ceftizoxime^{1 {21}}, and ceftriaxone^{1 {23}} are indicated in the treatment of female pelvic infections caused by susceptible organisms.

Perioperative infections (prophylaxis)— Cefamandole^{1 {04}}, cefazolin ^{{05} {63}}, cefonicid^{1 {09}}, cefotaxime ^{{11} {66}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, ceftriaxone ^{{23} {73}}, cefuroxime ^{{25} {58}}, [ cephalothin] ^{60}, and cephapirin ^{1 {29}} are indicated for the prophylaxis of perioperative infections caused by susceptible organisms.

Pharyngitis, bacterial (treatment) or
Tonsillitis (treatment)—Cefaclor ^{{01} {54}}, cefadroxil ^{{03} {62}}, cefdinir^{160}, cefditoren^1{175} cefixime ^{{08} {65}}, cefpodoxime^{1 {14}}, cefprozil ^{{15} {69}}, ceftibuten^{1 {20}}, cefuroxime axetil ^{{24} {74}}, cephalexin ^{{27} {59}}, and cephradine^{1 {30}} are indicated in the treatment of bacterial pharyngitis and tonsillitis caused by susceptible organisms.
—Penicillin is the usual medication of choice in the treatment of streptococcal infections, including the prophylaxis of rheumatic fever. These cephalosporins are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cephalosporins in the prevention of subsequent rheumatic fever are not available at present. ^{{01} {03} {08} {14} {15} {20} {24} {27} {30}{160}}

Pneumonia, bacterial (treatment)—Cefaclor ^{{01} {54}}, [cefadroxil] ^{62}, cefamandole ^{{04} {55}}, cefazolin ^{{05} {56} {155}}, cefdinir^{160}, cefepime ^{{161} {64}}, cefotaxime ^{{11} {66} {155}}, cefoxitin ^{{13} {68}}, cefpodoxime^{1 {14} {155}}, [cefprozil]^{1 {155}}, ceftazidime ^{{17} {71}}, ceftriaxone^{1 {23} {155}}, cefuroxime ^{{25} {58} {155}}, [cefuroxime axetil] ^{{74} {155}}, [cephalothin] ^{60}, and cephradine^{1 {30}} are indicated in the treatment of bacterial pneumonia caused by susceptible organisms.

Pulmonary infections, in cystic fibrosis (treatment)—[Cefaclor] ^{54}, [ cefamandole] ^{55}, and ceftazidime ^{1 {17}} are indicated in the treatment of pulmonary infections due to susceptible organisms in patients with cystic fibrosis.

Septicemia, bacterial (treatment)—Cefamandole ^{{04} {55}}, cefazolin ^{{05} {56}}, [cefepime] ^{64}, cefonicid^{1 {09}}, cefoperazone^{1 {10}}, cefotaxime ^{{11} {66}}, [cefotetan ]¹ , cefoxitin ^{{13} {68}}, ceftazidime ^{{17} {71}}, ceftizoxime ^{{21} {72}}, ceftriaxone ^{{23} {73}}, cefuroxime^{1 {25}}, [cephalothin] ^{60}, cephapirin^{1 {29}}, and [ cephradine]¹ are indicated in the treatment of bacterial septicemia caused by susceptible organisms.

Sinusitis (treatment)—Cefdinir^{160}, [ cefixime] ^{65}, cefprozil ^{{15} {69}}, and cefuroxime axetil ^{{24} {74}} are indicated in the treatment of sinusitis due to susceptible organisms.

Skin and soft tissue infections (treatment)—Cefaclor ^{{01} {54}}, cefadroxil ^{{03} {62}}, cefamandole ^{{04} {55}}, cefazolin ^{{05} {56}}, cefdinir^{160}, cefditoren^1{175}, cefepime ^{{161} {64}}, [ cefixime]¹ , cefonicid^{1 {09}}, cefoperazone^{1 {10}}, cefotaxime ^{{11} {66}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, cefpodoxime^{1 {14}}, cefprozil ^{{15} {69}}, ceftazidime ^{{17} {71}}, ceftizoxime ^{{21} {72}}, ceftriaxone ^{{23} {73}}, cefuroxime ^{{25} {58}}, cefuroxime axetil ^{{24} {74}}, cephalexin ^{{27} {59}}, [cephalothin] ^{60}, cephapirin^{1 {29}}, and cephradine^{1 {30}} are indicated in the treatment of skin and soft tissue infections caused by susceptible organisms.

Urinary tract infections, bacterial (treatment)— Cefaclor ^{{01} {54}}, cefadroxil ^{{03} {62}}, cefamandole ^{{04} {55}}, cefazolin ^{{05} {56}}, cefepime ^{{161} {64}}, cefixime ^{{08} {65}}, cefonicid^{1 {09}}, cefoperazone^{1 {10}}, cefotaxime ^{{11} {66}}, cefotetan ^{{12} {67}}, cefoxitin ^{{13} {68}}, cefpodoxime^{1 {14}}, [cefprozil] ^{69}, ceftazidime ^{{17} {71}}, ceftizoxime ^{{21} {72}}, ceftriaxone ^{{23} {73}}, cefuroxime ^{{25} {58}}, cefuroxime axetil^{1 {24}}, cephalexin ^{{27} {59}}, [cephalothin] ^{60}, cephapirin^{1 {29}}, and cephradine^{1 {30}} are indicated in the treatment of bacterial urinary tract infections caused by susceptible organisms.

Ventriculitis (treatment)—Cefotaxime ^{{11} {66}} is indicated in the treatment of ventriculitis caused by susceptible organisms.

[Endocarditis, bacterial (prophylaxis) ]¹—Cefadroxil ^{31}, cefazolin ^{31}, and cephalexin ^{31} are indicated in the prevention of bacterial endocarditis caused by susceptible organisms. However, cefazolin and cephalexin are not recommended for genitourinary tract procedures ^{149}.

[Melioidosis (treatment)]¹—Ceftazidime is indicated for the treatment of melioidosis^{{163}{164}{165}{166}{167}{168}{169}{170}{171}{172}}.
—Melioidosis is an infection with Burkholderia pseudomallei, previously known as Pseudomonas pseudomallei. It is endemic in areas of southeast Asia and the northern part of Australia. Melioidosis causes acute and chronic pulmonary disease, abscesses of the skin and internal organs, meningitis, brain abscess and cerebritis, and acute fulminant rapidly fatal sepsis. Infection with B. pseudomallei has a high mortality rate. It is more common among adults, individuals with diabetes, and individuals with chronic renal disease, but it can occur in normal hosts and children. Melioidosis can reactivate years after primary infection and result in chronic or acute life-threatening disease. Melioidosis should be considered as a potential diagnosis for any patient with exposure to areas of endemicity^{{163}{164}{165}{166}{167}{168}{169}{170}{171}{172}}.

[Sinusitis, amoxicillin-resistant (treatment)]¹—Cefaclor is used in the treatment of sinusitis resistant to amoxicillin.

Unaccepted
None of the cephalosporins is considered to be effective against enterococci, Listeria species, chlamydia, Clostridium difficile , or methicillin-resistant Staphylococcus epidermidis or S. aureus . ^{89}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Table 1. Pharmacology/Pharmacokinetics ^{32}

Drug	Bioavailability (%)	Half-life (hr)		Time to peak serum concentration (hr)	Peak serum concentration after dose		Peak urine concentration after dose
		Normal renal function	Impaired renal function		mcg/mL	Dose	mcg/mL	Dose
First generation
Cefadroxil	95	1.5	20–25
Oral				1.5–2	16	500 mg	1800	500 mg
					28	1 gram
Cefazolin		1.4–2 *	40–70
IM					17	250 mg	2400	500 mg
					38	500 mg	4000	1 gram
					64	1 gram
IV				End of infusion	188	1 gram
Cephalexin	95	0.9–1.5	20–40
Oral				1–2	9	250 mg	1000	250 mg
					18	500 mg	2200	500 mg
					32	1 gram	5000	1 gram
Cephalothin		0.5–1 †	3–18
IM				0.5	10	500 mg	800	500 mg
					20	1 gram	2500	1 gram
IV				0.25–0.5	30	1 gram
					80–100	2 grams
Cephapirin		0.5–0.8	1.5–2.7
IM				0.5–1	9	500 mg	900	500 mg
					16	1 gram
IV				End of infusion	35	500 mg
					67	1 gram
					129	2 grams
Cephradine	95	1.3	6–15
Oral				1 ‡	9	250 mg	1600	250 mg
					17	500 mg	3200	500 mg
					24	1 gram	4000	1 gram
Second generation
Cefaclor	95	0.6–0.9	2.3–2.8
Capsules, oral suspension				0.5–1 ‡	7	250 mg	600	250 mg
					13	500 mg	900	500 mg
					23	1 gram	1900	1 gram
Extended-release tablets				2.5–2.7	3.7 §	375 mg
					8.2 §	500 mg
Cefamandole		0.5–1.2	3–11
IM				0.5–2	13	500 mg	254	500 mg
					25	1 gram	1357	1 gram
IV				End of infusion	139	1 gram	750	1 gram
					240	2 grams	1380	2 grams
					533	3 grams
					666	4 grams
Cefonicid		3.5–4.5	17–56
IM				1	99	1 gram	385	500 mg
IV				End of infusion	220	1 gram
Cefotetan		3–4.6	Prolonged
IM				1–3	71	1 gram
					91	2 grams
IV				End of infusion	158	1 gram	1700	1 gram
					237	2 grams	3500	2 grams
Cefoxitin		0.7–1.1 #	13–20
IV				End of infusion	110	1 gram
					244	2 grams
Cefprozil	90–95	1.3 **	5–6
Oral				1.5–1.7	6.1	250 mg	700	250 mg
					10.5	500 mg	1000	500 mg
					18.3	1 gram	2900	1 gram
Ceftibuten		2–2.6 ††	7–22
Oral				1.7–3 ††	10 ††	200 mg ††
					15	400 mg
					23	800 mg
Cefuroxime		1.2–1.9 ‡‡	3–17
Oral suspension				2.7–3.6	3.3	10 mg/kg
					5.1	15 mg/kg
					7	20 mg/kg
Tablet	After food §§ (52–68)			2.2–3	2	125 mg
					4	250 mg
	Fasting (37)				7	500 mg
					13.6	1 gram
IM				0.75	27	750 mg	1300	750 mg
IV				End of infusion	50	750 mg	1150	750 mg
					100	1.5 grams	2500	1.5 grams
Third generation
Cefdinir		1.7	3–9
Oral capsule	16–21			3	1.6	300 mg
					2.9	600 mg
Oral suspension	25			1.8–2.2	2.3	7 mg/kg
					3.9	14 mg/kg
Cefditoren		1.6
Tablets				1.5 to 3 hours	1.8 mcg per mL	200 mg
Cefixime	40–50	3–4	6.4–11.5
Oral				2–6	1.3	100 mg	73	100 mg
					3.5–4.4	400 mg	164	400 mg
Cefoperazone		1.6–2.4 ##	2.1 ##
IM				1–2	65–75	1 gram	1000	2 grams
					97	2 grams
IV				End of infusion	153	1 gram	> 2200	2 grams
					252	2 grams
					340	3 grams
					506	4 grams
Cefotaxime	90–95	1	2.6–3
IM				0.5	12	500 mg
					21	1 gram
IV					39	500 mg
					102	1 gram
					214	2 grams
Cefpodoxime	50 §§	2.1–2.8	3.5–9.8
Oral				2–3	1.4	100 mg
					2.3	200 mg
					3.9	400 mg
Ceftazidime		1.4–2	13
IM				1	17	500 mg	2100	500 mg
					39	1 gram
IV				End of infusion	42	500 mg	12,100	2 grams
					69	1 gram
					170	2 grams
Ceftizoxime		1.4–1.7	30
IM				1	14	500 mg
					39	1 gram
IV				End of infusion	60	1 gram	> 6000	1 gram
					132	2 grams
					220	3 grams
Ceftriaxone
IM		5.8–8.7	12–24	2–3	38	500 mg	425	500 mg
					76	1 gram	628	1 gram
IV		4.3–4.6 ***		End of infusion	82	500 mg	526	500 mg
					151	1 gram	995	1 gram
					257	2 grams	2692	2 grams
Fourth generation
Cefepime	100	2	14
IM				1–2	14	500 mg
					30	1 gram
					57	2 grams
IV				End of infusion	18	250 mg
					39	500 mg
					82	1 gram
					164	2 grams

^* The half-life of cefazolin in neonates less than 1 week old is 4.5 to 5 hours.
^† The half-life of cephalothin in neonates less than 1 week old is 1.5 to 2 hours.
^‡ Delayed in presence of food.
^§ With food. Peak serum concentration is decreased when administered under fasting conditions.
^#  The half-life of cefoxitin is 5.6 hours in neonates 0 to 7 days of age; 2.5 hours in neonates 7 days to 1 month of age; and 1.7 hours in infants 1 to 3 months of age.
^** In children, the half-life of cefprozil is 1.8 to 2.1 hours.
^†† In children, the half-life of ceftibuten is 1.4 to 2.6 hours; the time to peak serum concentration is 2 hours; and the peak serum concentration is 13 mcg/mL after a dose of 9 mg/kg. In geriatric patients, the peak serum concentration is 17 mcg/mL after a dose of 200 mg.
^‡‡ In neonates, the half-life of cefuroxime can be three to five times longer than it is in adults.
^§§ Bioavailability is increased when this medication is administered with food.
^## In adults, not significantly different from normal values during hemodialysis; 2.8 to 4.2 hours between hemodialysis periods; 3 to 7 hours with impaired hepatic function and/or biliary obstruction. In pediatric patients, 6 to 10 hours in low-birth-weight neonates; 4 to 6 hours in infants approximately 1 month of age; 2.2 hours in infants and children 2 months to 11 years of age.
^*** The half-life of ceftriaxone in pediatric patients with meningitis after a 50- or 75-mg-per-kg dose.

Table 2. Pharmacology/Pharmacokinetics ^{* {33}}

Drug	Protein binding (%)	Hepatic and renal biotransformation (%)	Renal excretion (% unchanged/hr)	Vol D (L/kg)	Removal by dialysis
					HD	PD
First generation
Cefadroxil	Low (15–20)	No	93/24 (GF; TS)	0.31	Yes
Cefazolin	High (85)	No	60–89/6; 70-86/24 (GF; TS)	0.12	Moderate	No
Cephalexin	Low (10–15)	No	80/6; 90/8 (TS; GF)	0.26	Moderate	Yes
Cephalothin	Moderate (70)	Yes; 20–30	60–70/6 (30 as metabolite/6) (TS)	0.26	Moderate
Cephapirin	Moderate (44–50)	Yes; 40	70/6 (TS; GF; TR)	0.13	Slight
Cephradine	Very low to low (8–17)	No	60–90/6 (TS)	0.25	Signif	Yes
Second generation
Cefaclor	Low (25)	No	60–85/8	0.35	Moderate	Yes
Cefamandole	High (70–80)	No	65–85/8 (GF; TS)	0.16	Moderate	Slight
Cefonicid	Very high (> 90)	No	99/24	0.11	Slight
Cefotetan	High to very high (78–91)	No	50–80/24	0.19	Slight	NS
Cefoxitin	High (70–80)	Slight; 0.2–5 (inactive metabolite)	85/6 (GF; TS)	0.16	Moderate	NS
Cefprozil	Moderate (36–45)	No	60–70/8	0.17–0.23	Moderate
Ceftibuten	High (65–77)		95/24	0.21 †	Yes
Cefuroxime	Low to moderate (33–50)			0.82	Moderate
Oral		No; prodrug rapidly hydrolyzed to cefuroxime	50/12 (GF; TS)
IM, IV			90/6; 96/24
Third generation
Cefdinir	High (60–70)	No	12–18/ 1.7	0.35 ‡
Cefditoren	High (88)	Pivoxil salt hydrolyzed to active cefditoren		9.3 L	30%
Cefixime	High (65)	No	16/24	0.11	NS	No
Cefoperazone	High to very high (82–93)	No	20–30/12 § (GF)	0.14–2	Slight
Cefotaxime	L