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  (µg/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  (µg/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 influenzaea	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 amoxicillin’s 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 µg/mL

highly resistant strains have MICs of ³2.0 µg/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 µg/mL	na	0.5	50-60
penicillin G oral3	400,000 u	0.3 µg/mL	15-30	0.5
penicillin VK	250 mg	3 µg/mL	60	0.5	75-85
procaine pen G IM	300,000 u	0.9 µg/mL
benzathine pen G IM	1.2 mu	0.09 µg/mL
Penicillinase-resistant penicillins
nafcillin  IV	1g	20 µg/mL	na	0.5-1.0	90
oxacillin IV	500mg	52-63µg/mL	na	0.5-0.7	94
oxacillin oral	500mg	5-7 µg/mL	30-35%	0.5-0.7
cloxacillin oral	500mg	7.5-14µg/mL	50	0.5	95
dicloxacillin oral	500mg	10-17µg/mL	37	0.8	98
Aminopenicillins
ampicillin IV	1g	40 µg/mL	na	1-1.3	20
ampicillin oral	1g	3 µg/mL	30-50	1-1.3
amoxicillin oral	1g	7.5 µg/mL	80	1-1.3	20
Extended-spectrum penicillins
carbenicillin IV	3g	223 µg/mL	na	1.1	50
carbenicillin oral	1g	9 µg/mL	30
ticarcillin	3.5g	210 µg/mL	na	1.2	45
mezlocillin	3g	263 µg/mL	na	0.8	16-42
piperacillin	4g	240 µg/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 ³ 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 ³27 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 ³ 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 ³ 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 ³ 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	³ 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 ³ 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 ³40 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 ³ 1 week and < 1 month: 75 mg/kg q6-8 hrs ³ 1 month and < 12 yrs: 50-75 mg/kg q4h ³ 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.