Page 85 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART I Basic Bacteriology
74
1
TABLE 10–4 Activity of Selected Cephalosporins
Generation of
Drug
Clinically Useful Activity
Cephalosporin
Gram-positive cocci such as staphylococci and streptococci except enterococci and MRSA
Cefazolin, cephalexin
First
Bacteroides fragilis
Cefoxitin

Enteric gram-negative rods such as Escherichia coli, Klebsiella and Proteus. Also Neisseria gonorrhoeae
Third
Ceftriaxone
Second Cefuroxime Haemophilus influenzae
Pseudomonas aeruginosa and other enteric gram-negative rods
Ceftazidime
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Enteric gram-negative rods that produce extended-spectrum β-lactamases; Staphylococcus aureus (not
Fourth
Cefepime
MRSA) and penicillin-resistant Streptococcus pneumoniae
Fifth
Ceftaroline
Gram-positive cocci and gram-negative rods that cause bacterial pneumonia and gram-positive cocci
that cause skin infections including MRSA

Enteric gram-negative rods that produce extended-spectrum β-lactamases; Pseudomonas aeruginosa;
Ceftolozane
used in combination with tazobactam
MRSA = methicillin-resistant Staphylococcus aureus.
1
The spectrum of activity is intentionally incomplete. It is simplified for the beginning student to illustrate the expanded coverage of gram-negative organisms with successive
generations and does not cover all possible clinical uses.
β-Lactamase inhibitors such as tazobactam and avibactam
by gram-negative rods that produce extended-spectrum
are combined with certain cephalosporins to prevent inac-
β-lactamases that make them resistant to all penicillins and
tivation of the cephalosporin. For example, the FDA has Imipenem is especially useful in treating infections caused
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cephalosporins. Carbapenems are often the “drugs of last
approved the combination of ceftazidime/avibactam (Avy-
resort” against bacteria resistant to multiple antibiotics.
caz) and ceftolozane/tazobactam (Zerbaxa) for the treat-
Imipenem is prescribed in combination with cilastatin,
ment of intra-abdominal infections and complicated
urinary tract infections caused by antibiotic-resistant
that inactivates imipenem. Imipenem is not inactivated by
gram-negative rods.
most β-lactamases; however, carbapenemases produced by
K. pneumoniae that degrade imipenem and other car-
Carbapenems
bapenemases have emerged. Other carbapenems, such as
Carbapenems are β-lactam drugs that are structurally dif-
ertapenem and meropenem, are not inactivated by dehy-
ferent from penicillins and cephalosporins. For example,
dropeptidase and are not prescribed in combination with
imipenem (N-formimidoylthienamycin), a commonly used
carbapenem, has a methylene group in the ring in place of
the sulfur (Figure 10–4). Imipenem has one of the widest
Monobactams
spectrums of activity of the β-lactam drugs. It has excellent cilastatin.
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Monobactams are also β-lactam drugs that are structurally
bactericidal activity against many gram-positive, gram-
different from penicillins and cephalosporins. Mono-
negative, and anaerobic bacteria. It is effective against most
bactams are characterized by a β-lactam ring without an
gram-positive cocci (e.g., streptococci and staphylococci),
most gram-negative cocci (e.g., Neisseria), many gram-
monocyclic) (see Figure 10–4). Aztreonam, currently the
negative rods (e.g., Pseudomonas, Haemophilus, and mem-
most useful monobactam, has excellent activity against
bers of the family Enterobacteriaceae such as E. coli), and
many gram-negative rods, such as Enterobacteriaceae and
various anaerobes (e.g., Bacteroides and Clostridium).
CH
3
O
N
COOH
C
CH
C
NH
3
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CH
S
3
CONH
NHC
N
H
2
S
COOH
N
SO
O
3
B
FIGURE 10–4
A: Imipenem. B: Aztreonam.
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