Figure. Penicillin Structure

 

 

 

 

A thiazolidine ring;  B beta-lacam ring; R1- acyl side chain

 

 

Table 1. Classification of Penicillins 

Class and compounds 

 Trade names1     

Availability

Natural penicillins

 

 

penicillin G potassium

Pfizerpen

Parenteral: 5, 20 mu vials

phenoxymethyl penicillin

various generics

Tablets: 250, 500mg

Solution: 125mg/5 mL, 250mg/5 mL

penicillin G procaine

Wycillin  

Parenteral: 600,000 u/mL

penicillin G benzathine

Bicillin L-A, Permapen

Parenteral: 300,000u/mL, 600,000u/mL

penicillin G procaine/ penicillin G benzathine combination

Bicillin C-R 

Parenteral: 150,000u/150,000 u/mL, 150,000/450,000 u/mL, 300,000/30,000 u/mL

Penicillinase-Resistant Penicillins

 

 

methicillin

Staphcillin

no longer available

nafcillin

various generics

Parenteral: 20 mg/mL vials

oxacillin

Bactocill 

Capsules: 250, 500mg

Solution: 250mg/5mL

Parenteral: 500mg, 1, 2, 4 g vials

cloxacillin

various generics

Capsules: 250, 500mg

Solution: 125mg/5 mL

dicloxacillin

Dynapen

Capsules: 250, 500mg

Suspension: 62.5 mg/5 mL

Aminopenicillins

 

 

ampicillin

Principen

Capsules: 250, 500 mg

Suspension: 125 mg/5 mL, 250 mg/5 mL

Parenteral: 125, 250, 500 mg, 1, 2 g vials

amoxicillin

Amoxil,   Trimox

Capsules: 250, 500 mg

Chewable tablets: 125, 250, 400 mg

Film-coated tablets: 500, 875 mg

Suspension: 50mg/mL, 125 mg/5 mL, 200 mg/5 mL,

250 mg/5 mL, 400 mg/5 mL

bacampicillin 

Spectrobid 

no longer available

Carboxypenicillins

 

 

carbenicillin

Geocillin

Tablets: 382 mg

ticarcillin

Ticar

Parenteral: 1, 3, 6 g vials

Ureidopenicillins and piperazine penicillin

 

 

azlocillin

Azlin

no longer available in U.S. market

mezlocillin    

Mezlin

no longer available in U.S. market

piperacillin

Pipracil  

Parenteral:  2, 3, 4g vials

1 = not all formulations are available with every brand
 

 

Table 2.   Minimal Inhibitory Concentrations (MIC50) of Specific Organisms 

  MIC-50  (g/mL)
Organism Penicillin G Penicillin V Oxacillin Ampicillin Amoxicillin

Ticarcillin

Mezlocillin

Piperacillin

Gram-Positive aerobes            
Enterococcus sp. 2.0 4.0 >32 0.5 64 2
Staphylococcus aureus            
   (Non Penicillinase producing) 0.03 0.03 0.4 0.06 1.0 0.06
   (Penicillinase-producing) >32 >32 1.6 >32 32 32
Staphlyococcus epidermidis  0.02 0.02 0.2 0.05 1.0  1.0
Streptococcus pneumoniae 0.01 0.01 0.1 0.02 0.4 0.02
Viridans streptococci 0.01 0.01 0.2 0.05 0.5 0.25
Streptococcus pyogenes 0.015 0.015 0.04 0.03 0.25 0.125
Listeria monocytogenes 0.25 0.25 >4 0.25 4 0.5
Gram-negative aerobes            
Neisseria gonorrhoeaea 0.25   1.0 0.06 0.03 0.015
Neisseria meningitidis 0.03   0.06 0.06 0.03 0.03
Escherichia coli  64 128 8 2 4 2
Proteus mirabilis 32 128 4 0.5 2 1
Indole + P. mirabilis >500  >500 >128 64 4 1
Hemophilus influenzaea 0.4 6.3 25 0.25 0.012 0.03
Salmonella sp. 8 128 2 1 2 2
Shigella sp. 16 64   4    
Serratia marcescens >128 >128 >128 >500 16 88
Klebsiella sp. >128 >128 >128 64 >64 16
Enterobacter sp. >128 >128 >128 128 16 8
Citrobacter sp. >128 >128 >128 32 2 2
Acinetobacter sp. >128 >128 >128 16 8 16
Pseudomonas aeruginosa >128 >128 >128 >500 16 8
Anaerobes            
Peptostreptococcus 0.1   >32 0.5 0.5 0.5
Fusobacterium nucleatum <0.1   >64 <0.1 0.5 <0.1
Clostridium perfringens 0.5    >64 <0.1 0.5 0.5
Bacteroides fragilis 16   >64 16  16 32

a non-beta-lactamase producing strains

 

Table 3. Minimal  Inhibitory Concentrations (MIC-90) of Specific Organisms 

 

MIC-90  (g/mL)

Organism

 Penicillin G  

Oxacillin

Ampicillin Amoxicillin

Ticarcillin

Mezlocillin

Piperacillin

Gram-Positive aerobes

 

 

 

 

 

Enterococcus sp.

2.0

>100

4

128

4

Staphylococcus aureus

 

 

 

 

 

   (Non Penicillinase producing) 

0.03

3.1

0.125

1.0

0.06

   (Penicillinase-producing)

>32

6.3

>32

32

32

Staphlyococcus epidermidis

 

 

 

1.0

1.0

Streptococcus pneumoniae

0.03

0.8

0.02

1

0.02

Viridans streptococci

 

 

 

8

0.25

Streptococcus pyogenes

0.015

0.4

0.03

0.25

0.125

Listeria monocytogenes

0.5

>4

0.5

4

0.5

Gram-negative aerobes

 

 

 

 

 

Neisseria gonorrhoeaea

0.5

12.5

0.06

0.03

0.015

Neisseria meningitidis

0.06

6.3

0.25

0.03

0.03

Escherichia coli

64

>128

>256

>256

256

Proteus mirabilis 

32

>128

>256

128

16

Indole + P. mirabilus 

>500

>128

>256

>256

64

Hemophilus influenzae

4

100

0.5

0.25

 0.5

Salmonella sp.

16

>128

>256

>256

>256

Shigella sp.

32

 

 

 

 

Serratia marcescens 

>128

>128 

>128 

>256

128

Klebsiella sp.

>128

>128 

>128 

500

16

Enterobacter sp.

>128

>128 

>128 

>256

128

Citrobacter sp.

>128

>128

128

256

8

Acinetobacter sp.

>128

>128

64

64

128

Pseudomonas aeruginosa

>128 

>128

>128

128

32

Anaerobes

 

 

 

 

 

Peptostreptococcus

1.0 

>32

8.0

2.0

4.0

Fusobacterium nucleatum

1.0

>64

16.0

0.5

0.5

Clostridium perfringens

 0.5

>64

<0.1b   

0.5

0.5

Bacteroides fragilis

>64

>64

>64

128

128

a non-beta-lactamase producing strains

b amoxicillins MIC90 is 0.5.


 

Table 4. In Vitro Post-Antibiotic Effect of Selected Penicillins

 

S. aureus

S. pneumoniae

E. faecalis 

penicillin G

2-3.5 hrs

2.5-3.5 hrs

2.5-3.5 hrs

ampicillin

2-2.5 hrs

2-6 hrs

0.5-2.5 hrs

nafcillin

1.5-2 hrs

ND

ND

piperacillin

0.5 hr

ND

0.5 hr

ND = no data


 

Table 5. Prevalence of Resistance of Organisms to Penicillins

Organism

Prevalence

Gram-positive

 

Streptococcus pneumoniaea,b

Intermediate pcn resistance 11-28%

Highly pcn resistant 11-33%

Staphylococcus aureus

Pcn resistant >95%

Methicillin resistant (nosocomial) 23-38%

Gram-negative

 

Haemophilus influenzae

ampicillin 1-64%

Moraxella catarrhalis

up to 85%

Escherichia coli

ampicillin 30-50%

Neisseria gonorrhoeae

1.2-38%

Neisseria meningitidis

up to 20%

Extended-spectrum beta-lactamase producers

 

Klebsiella pneumoniae

up to 24%

Pseudomonas aeruginosa

piperacillin 5-30%

a           intermediate resistant strains have MICs of 0.12-1.0 g/mL

highly resistant strains have MICs of 2.0 g/mL

b           United States data

  

 

Table 6. Pharmacokinetic Properties of  Penicillins

Drug

dose

peak serum

conc.1

% bioavailability

half-life 

(hours) 

%ppb2

Natural penicillins

 

 

 

 

 

benzylpenicillin

2g

20 g/mL 

na

0.5

50-60

penicillin G oral3

400,000 u

0.3 g/mL

15-30

0.5

 

penicillin VK

250 mg

3 g/mL

60

0.5

75-85

procaine pen G IM

300,000 u

0.9 g/mL

 

 

 

benzathine pen G IM

1.2 mu

0.09 g/mL  

 

 

 

Penicillinase-resistant penicillins

 

 

 

 

 

nafcillin  IV

1g

20 g/mL

na

0.5-1.0

90

oxacillin IV

500mg

52-63g/mL

na

0.5-0.7

94

oxacillin oral

500mg

5-7 g/mL

30-35%

0.5-0.7

 

cloxacillin oral

500mg

7.5-14g/mL

50

0.5

95

dicloxacillin oral

500mg

10-17g/mL

37

0.8

98

Aminopenicillins

 

 

 

 

 

ampicillin IV

1g

40 g/mL

na

1-1.3 

20

ampicillin oral

1g

 3 g/mL

30-50

1-1.3

 

amoxicillin oral

1g

7.5 g/mL

80

1-1.3

20

Extended-spectrum penicillins

 

 

 

 

 

carbenicillin IV

3g

223 g/mL

na

1.1

50

carbenicillin oral

1g

9 g/mL

30

 

 

ticarcillin

3.5g

210 g/mL

na

1.2

45

mezlocillin

3g

263 g/mL

na

0.8 

16-42

piperacillin

4g

240 g/mL

na

1.0

16

                                                                                    

1 = data complied from product package information and Donowitz 1988.

2 = % plasma protein bound

3 = no longer commercially available in the US
 

 

Table 7.  Guidelines for Adult and Pediatric Dosing of Penicillins

Drug

Normal adult dosec 

Normal pediatric dosec 

Dosage adjustment in renal impairmentd,e

Natural penicillins

 

 

 

benzylpenicillin (penicillin G)

enterococcal endocarditis: 4-6 mub IV q4h

Streptococcal meningitis: 2-3 mu IV q4h

Streptococcal infection: 2mu IV q4-6h

1week and > 2kg: 20,000-50,000 u/kg IV q8h

1 week and 2kg: 20,000-50,000 u/kg IV q12h

> 1 week and 2kg: 25,000-65,000 u/kg IV q8h

> 1 week and > 2kg: 25,000-65,000 u/kg IV q6h

> 1month and < 12 years, severe infection: 40,000-60,000 u/kg IV q4-6h

> 12 years: usual adult dose 

CrCL 10-50 mL/min:

Increase dosing interval to q6-8h

CrCL < 10 mL/min:

Increase dosing interval to q12h

 

anthrax (setting of bioterrorism): 4 mg IV q4h

<12 years: 50,000 u/kg IV q6h

>12 years:  usual adult dose

 

 

neurosyphilis: 3-4 mu IV q4h

 

 

penicillin VK

Streptococcal pharyngitis: 500 mg po bid-tid for 10 days

Lyme disease: 250-500mg po qid for 10-30 days

> 1 month: 15-62.5 mg/kg/day po in 3-6 divided doses

Lyme disease and < 9 years: 25-50 mg/kgday po in 3 divided doses for 10-30 days

Little data available.

Adjust dose if CrCL < 10 mL/min.

procaine penicillin G (PPG)

Streptococcal infection: 600,000-1.2 mu IM qd for 10 days

neonates: 50,000 u/kg/day IM

>1 month and < 12 years:  25,000-50,000 u/kgday IM

12 years: usual adult dose

Not necessary

benzathine penicillin G

early syphilis: 2.4 mu IM

group A strep infection and prophylaxis of recurrent rheumatic fever: 1.2 mu IM

<27kg: 300,000-600,000 u IM

27 kg: 1.2 mu IM

Not necessary

Penicillinase-resistant penicillins

 

 

 

nafcillin

500mg-1g po q4-6h

1-2g IV q4-6h

> 1 month: 50-100 mg/kg/day po in 3-4 divided doses

> 1 month: IV data limited, 100-200mg/kg/day  in 4-6 divided doses

CrCL < 10 mL/min:

Extend dosage interval to q8-12 hrs

oxacillin

500mg-1g po q4-6h

1-2g IV q4-6h

 > 1 month and < 40kg: 50-100 mg/kg/day po

or IV in 4 divided doses

40 kg: usual adult dose

CrCL < 10 mL/min:

use  lower range of usual dose

cloxacillin

 250-500mg po q6h

> 1 month and < 20 kg: 50-100 mg/kg/day po in 4 divided doses

20 kg: usual adult dose

 

dicloxacillin

125-250 mg po q6h

> 1 month and < 40 kg: 12.5 - 25 mg/kg/day po in 4 divided doses

40 kg: usual adult dose

Staphylococcal osteomyelitis: 50-100 mg/kg/day in 4 divided doses

not necessary

Aminopenicillins

 

 

 

ampicillin

250-500mg po q6h

1-2g IV q4h

1 month and < 40 kg: 50-200 mg/kg day IV in 4-6 divided doses

< 1 week: 25 mg/kg IV/IM q 8-12h

1 week and < 1 month: 25 mg/kg IV/IM q6-8h

> 40 kg: usual adult dose

CrCL 10-50 mL/min:

Extend dosing interval to q 6-12h

CrCL < 10 mL/min:

Extend dosing interval to q8-16h

amoxicillin

500mg po q12h or

250-500mg po q8h or

875mg po q12h

> 1 month and < 20 kg: 20-40 mg/kg/day in 3 divided doses

 > 20 kg: usual adult dose 

CrCL 10-50 mL/min:

Consider extending dosing interval to q12h.

CrCL < 10 mL/min:

Extend dosing interval to q12-24h.

Extended-spectrum penicillins

 

 

 

carbenicillin

382-764 mg po qid 

No data 

No data

ticarcillin

3g IV q4h 

> 1 month and < 40 kg: 100-300 mg/kg/day in 4-6 divided doses

40 kg: usual adult dose

CrCL 30-60 mL/min: 2g q4h

CrCL 10-30 mL/min: 2g q8h

CrCL < 10 mL/min: 2g q12h

Supplement after HD: 3g

mezlocillin

3-4g IV q4-6h

< 1 week: 75 mg/kg  q12h

1 week and < 1 month: 75 mg/kg q6-8 hrs

1 month and < 12 yrs: 50-75 mg/kg q4h

12 years: usual adult dose

CrCL 10-50 mL/min: 1.5-3g q6-8h

CrCL < 10 mL/min: 1.5-2g q8h

Supplement after HD: 3-4g

piperacillin

3-4g IV q4-6h

 1 month -12 years: 50 mg/kg q4h

CrCL 20-40 mL/min: 3-4g q8h

CrCL < 20 mL/min: 3-4g q12h

Supplement after HD: 1g

a = intramuscular

b = million units

c = These dosages are ranges of acceptable doses.  The lower range of usual dose is generally used for mild infection, upper range for severe infection (e.g. meningitis, endocarditis).  Higher dosages than recommended may be used in certain circumstances.  Clinical judgment should be used when dosing and prescribing information for the specific drugs should be consulted for more information.

d = clinical judgment should be utilized when making decisions regarding dosage adjustment in renally impaired patients, taking into account severity of renal impairment, site of infection, expected length of therapy, organism isolated, etc.

e = data complied using McEvoy 2003 AHFS Drug Information and product package inserts

HD = hemodialysis


 

Table 8.  Approximate Cost of Typical Therapeutic Regimens of Selected Penicillins1

 

Drug

Dosing regimen

Cost1

Oral agents

 

 

ampicillin

500mg po q6h x 10d

$5.00

penicillin VK

500mg po q8h x 10d

$4.00

amoxicillin

500mg po q8h x 10d

$5.00

Long-acting agents

 

 

procaine penicillin G

1.2 mu IM x1

$5.00

benzathine penicillin G

2.4mu IM x1

$15.00

Intravenous agents

 

 

ampicillin

2g IV q4h x 10d

$57.00

penicillin G potassium

2 mu IV q4h x 10d

$21.00

penicillin G sodium

2 mu IV q4h x 10d

$158.00

oxacillin

1g IV q6h x 10d

$109.00

ticarcillin

3g IV q4h x 10d

$375.00

piperacillin

4g IV q6h x 10d

$390.00

1 = drug acquisition costs for Albany Medical Center Hospital, Albany, New York.
 

 

Table 9. Dosing During Continuous Renal Replacement Therapy (Oxacillin and Nafcillin)

CVVH (Continuous venovenous hemofiltration): 2g IV q4-6h

CVVHD (Continuous venovenous hemodialysis): 2g IV q4-6h

CVVHDF (Continuous venovenous hemodiafiltration) 2g IV q4-6h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which

combine dialysis with fluid removal.