This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
The antibiotics known as cephalosporins were first discovered and isolated in 1948
from Cephalosporium acremonium, in sewage remnants off of the Sardinian coast . They are mem-
bers of the class of antibiotics known as ß-lactams. Cephalosporins are a type of antibiotic in the
same class as penicillins (ß-lactams), but have a broader spectrum than penicillins, meaning they
can be used to treat more types of bacteria.
Evolution of Cephalosporins
Cephalosporin C, was the first cephalosporin to be isolated. The drug showed very low antibacterial
activity due to low potency. However, it was resistant to ß-lactamases and consequently, appeared to
be effective against penicillin-resistant cultures [2].
As scientists continued to investigate these drugs, they realized that enzymatic and chemical
techniques could be used to take Cephalosporin C and create the 7-amino-cephalosporanic acid (7-
ACA) core that is possessed by all cephalosporins. Consequently, this led to the creation of multiple
classes of cephalosporins that differed in spectrum, potency, ß-lactamase stability, and pharmacoki-
netic properties [2].
Of these classes, the third generation cephalosporins have played a significant role in treating bacte-
rial infections that are not responsive to penicillins or the first and second generations of cephalospor-
ins. These agents have exceptional activity against Gram-negative bacteria and Pseudomonas infec-tions and also can be useful in the treatment of multiresistant hospital infections. A few agents, like
ceftriaxone, are able to pass through the blood brain barrier into the cerebrospinal fluid. Conse-
quently, they are of use with some cases of bacterial meningitis. None of the first and second genera-
tion cephalosporins are able to pass through the blood brain barrier in levels that will produce a
therapeutic effect. The third generation agents are almost completely resistant to ß-lactamases, with
the exception of a few Gram-negative species of the enzymes. The two main downfalls of this group
of cephalosporins are their low antistaphylococci activity and high expense. However, overall they are
excellent agents that have made a considerable impact on the treatment of bacterial infections and
have demonstrated the importance of continuing research that will allow for the production of newer
and even more effective agents [1,7].
Classification
Cephalosporins are classified by 4 different generations, based partly on chronology of discovery, but
more so on their broadness of use. The first generation drugs are mostly active against gram positive
bacteria (Staphylococcus, Streptococcus, etc.). A common example of a first generation cepha-
losporin is cephalexin. The second generation drugs are more useful against gram negative bacteria
(Enterobacter, E.Coli, etc.). A common example of a second generation cephalosporin is cefuroxime
axetil. The third generation drugs are less active against the gram positive bacteria, but are more
active against gram negative than either the first or second generation.
Administration of cefprozil tablet or suspension formulation with food did not affect the extentof absorption (AUC) or the peak plasma concentration (Cmax) of cefprozil. However, there was
an increase of 0.25 to 0.75 hours in the time to maximum plasma concentration of cefprozil (Tmax).The bioavailability of the capsule formulation of cefprozil was not affected when administered 5 min-
utes following an antacid.
Plasma protein binding is approximately 36% and is independent of concentration in the
range of 2 mcg/ml to 20 mcg/ml.
There was no evidence of accumulation of cefprozil in the plasma in individuals with normal renal
function following multiple oral doses of up to 1000 mg every 8 hours for 10 days.
In patients with reduced renal function, the plasma half-life may be prolonged up to 5.2 hours depend-
ing on the degree of the renal dysfunction. In patients with complete absence of renal function, the
plasma half-life of cefprozil has been shown to be as long as 5.9 hours. The half-life is shortened
during hemodialysis. Excretion pathways in patients with markedly impaired renal function have not
been determined.
In patients with impaired hepatic function the half-life increases to approximately 2 hours. The magni-
tude of the changes does not warrant a dosage adjustment for patients with impaired hepatic func-
tion.
The average AUC observed in elderly subjects (> 65 years of age) is approximately 35-60% higher
relative to young adults, and the average AUC in females is approximately 15-20% higher than in
males. The magnitude of these age- and gender-related changes in the pharmacokinetics of cefprozil
is not sufficient to necessitate dosage adjustments.
Adequate data on CSF levels of cefprozil are not available.
Comparable pharmacokinetic parameters of cefprozil are observed between pediatric patients (6
months-12 years) and adults following oral administration of selected matched doses. The maximum
concentrations are achieved at 1-2 hours after dosing. The plasma elimination half-life is approxi-
mately 1.5 hours. In general, the observed plasma concentrations of cefprozil in pediatric patients at
the 7.5, 15, and 30 mg/kg doses are similar to those observed within the same time frame in normal
adult subjects at the 250, 500 and 1000 mg doses, respectively.
Mean (SD) Plasma Cefprozil Concentrations (mcg/ml)
The skin blister fluid half life estimate for Cefprozil were significantly longer than they were for com-
parator drugs. The level of cefprozil in skin blisters declined more slowly than plasma level[14].
Cefprozil appears to be as efficacious as amoxicillin/clavulanate or Cefaclor in case of skin and soft
tissue infection[15,16]
Middle ear fluid
Cefprozil achieves up to 8.67mcg/ml concentration in middle ear fluid [18]
INDICATIONS
Cefprozil is indicated for the treatment of patients with mild to moderate infections caused by suscep-tible strains of the designated microorganisms in the conditions listed below:
Upper Respiratory Tract
Otitis Media: caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-lactamase-
producing strains) and Moraxella (Branhamella) catarrhalis (including ß-lactamase-producing strains)
Acute Sinusitis: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-
lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including ß-lactamase-pro-
ducing strains).
Lower Respiratory Tract
Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic
Bronchitis: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including ß-lactamase-
producing strains), and Moraxella (Branhamella) catarrhalis, (including ß-lactamase-producing strains)
Skin and Skin Structure
Uncomplicated Skin and Skin-Structure Infections: Caused by Staphylococcus aureus (including
penicillinase-producing strains) and Streptococcus pyogenes.Abscesses usually require surgical drain-
age. Culture and susceptibility testing should be performed when appropriate to determine suscepti-
bility of the causative organism to cefprozil.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefprozil and
other antibacterial drugs, Cefprozil should be used only to treat or prevent infections that are proven
or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information
are available, they should be considered in selecting or modifying antibacterial therapy. In the absence
of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of
Safety and effectiveness in pediatric patients below the age of 6 months have not been established
for the treatment of otitis media or acute sinusitis, or below the age of 2 years for the treatment of
pharyngitis/tonsillitis or uncomplicated skin and skin structure infections. However, accumulation ofother cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age
group) has been reported.
Geriatric Use
Of the more than 4500 adults treated with CEFPROZIL in clinical studies, 14% were 65 years and
older, while 5% were 75 years and older. When geriatric patients received the usual recommended
adult doses, their clinical efficacy and safety were comparable to clinical efficacy and safety in
nongeriatric adult patients. Other reported clinical experience has not identified differences in re-
sponses between elderly and younger patients, but greater sensitivity of some older individuals to the
effects of CEFPROZIL cannot be excluded.
CEFPROZIL is known to be substantially excreted by the kidney, and the risk of toxic reactions to this
drug may be greater in patients with impaired renal function. Because elderly patients are more likely
to have decreased renal function, care should be taken in dose selection and it may be useful to
monitor renal function.
OVERDOSE
Single 5000 mg/kg oral doses of cefprozil caused no mortality or signs of toxicity in adult, weaning or
neonatal rats, or adult mice. A single oral dose of 3000 mg/kg caused diarrhea and loss of appetite in
cynomolgus monkeys, but no mortality.
Cefprozil is eliminated primarily by the kidneys. In case of severe overdosage, especially in patients
with compromised renal function hemodialysis will aid in the removal of cefprozil from the body.
CONTRAINDICATIONS
Cefprozil is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.
CLINICAL STUDIES
Study OneIn a controlled clinical study of acute otitis media performed in the United States where significant
rates of beta-lactamase producing organisms were found, cefprozil was compared to an oral antimi-
crobial agent that contained a specific beta-lactamase inhibitor. In this study, using very strict evaluability
criteria and microbiologic and clinical response criteria at the 10-16 days post-therapy follow-up, the
following presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) and safety
Cefprozil vs beta-lactamase inhibitor-containing control drug
Efficacy: Pathogen % of Cases with Pathogen (n=47) Outcome
S. pneumoniae 51.0% Cefprozil equivalent to control
H. influenzae 29.8% Cefprozil equivalent to control
M. catarrhalis 6.4% Cefprozil equivalent to control
S. pyogenes 12.8% Cefprozil equivalent to control
Overall 100.0% Cefprozil equivalent to control
Safety
The incidence of adverse events in the cefprozil arm was comparable to the incidence of adverse
events in the control arm (agent that contained a specific beta-lactamase inhibitor).
Study 3
Three recently completed clinical studies have demonstrated therapeutic advantages of cefprozil
over cefaclor and erythromycin in the treatment of skin and skin-structure infections. Specifically,cefprozil offers clinical efficacy equivalent to those of cefaclor and erythromycin both at lower total
doses and on a less frequent dosing schedule (once or twice daily vs. three to four times daily). The
advantage of once-daily or twice-daily dosing with cefprozil may contribute to patient convenience
and compliance.[1]
Study 4
In a multicenter study, 598 patients with skin or skin-structure infections were randomly assigned to
receive 500 mg of cefprozil once daily (or 20 mg/kg once daily) or 250 mg of cefaclor three times daily
(or 20 mg/kg daily in three equal doses) for 5 to 10 days. Treatment was evaluated in 212 cefprozil-
treated patients and in 210 cefaclor-treated patients. The patients were aged 2 to 99 years (mean, 28
years) and their primary diagnoses were impetigo (in 99 patients), pyoderma (in 98), superficial
abscess (in 70), and cellulitis (in 64). A satisfactory clinical response was found in 93%of the cefprozil-treated patients and in 92% of the cefaclor-treated patients, thepathogens were eradicated in 91% and 89%, and overall treatment was rated effective in
87% of both groups. Adverse clinical events were reported by 5% of the patients in both groups; one
cefprozil-treated patient and three cefaclor-treated patients withdrew from treatment because of ad-
verse events. It is concluded that cefprozil administered once daily is as effectiveand safe as cefaclor administered three times daily in the treatment of mild tomoderate skin and skin-structure infections[2].