Penicillins

1. Natural penicillins
natural penicillins are B-lactam antibiotics. Among the most important antibiotics, natural penicillins are the
preferred drugs in the treatment of many infectious diseases.
a. Available agents
(1) Penicillin G sodium and potassium salts can be administered orally, intravenously, or intramuscularly.
(2) Penicillin V (Pen-Vee K), a soluble drug form, is administered orally.
(3) Penicillin G procaine and penicillin G benzathine are repository drug forms. Administered intramuscularly, these
insoluble salts allow slow drug absorption from the injection site and thus have a longer duration of action (12 to 24
hrs).
Mechanism of action.
Penicillins are bactericidal; they inhibit bacterial cell wall synthesis in a manner similar to that of the cephalosporins
Spectrum of activity
(1) Natural penicillins are highly active against gram-positive cocci and against some gramnegative cocci.
(2) Penicillin G is 5 to 10 times more active than penicillin V against gram-negative organisms and some anaerobic
organisms.
(3) Because natural penicillins are readily hydrolyzed by penicillinases (b-lactamases), they are ineff ective against S.
aureus and other organisms that resist penicillin.
Uses
(1) Penicillin G is the preferred agent for all infections caused by penicillin-susceptible S. pneumoniae organisms,
including
(a) Pneumonia (b) Arthritis (c) Meningitis (d) Peritonitis (e) Pericarditis (f) Osteomyelitis (g) Mastoiditis
(2) Penicillins G and V are highly effective against other streptococcal infections, such as pharyngitis, otitis media,
sinusitis, and bacteremia.
(3) Penicillin G is the preferred agent in gonococcal infections, syphilis, anthrax, actinomycosis, gas gangrene, and
Listeria infections.
(4) Administered when an oral penicillin is needed, penicillin V is most useful in skin, soft tissue, and mild respiratory
infections.
(5) Penicillin G procaine is effective against syphilis and uncomplicated gonorrhea.
(6) Used to treat syphilis infections outside the CNS, penicillin G benzathine also is effective against group A B-
hemolytic streptococcal infections.
(7) Penicillins G and V may be used prophylactically to prevent streptococcal infection, rheumatic fever, and
neonatal gonorrheal ophthalmia. Patients with valvular heart disease may receive these drugs preoperatively.
(8) There is emerging resistance to penicillin G by S. pneumoniae in some areas of the United States. The alternative
therapy is vancomycin.
Side Effect
(1) Hypersensitivity reactions. These occur in up to 10% of patients receiving penicillin. Manifestations range from
mild rash to anaphylaxis.
(a) The rash may be urticarial, vesicular, bullous, scarlatiniform, or maculopapular. Rarely, thrombopenic purpura
develops.
(b) Anaphylaxis is a life-threatening reaction that most commonly occurs with parenteral administration. Signs and
symptoms include severe hypotension, bronchoconstriction, nausea, vomiting, abdominal pain, and extreme
weakness.
(c) Other manifestations of hypersensitivity reactions include fever, eosinophilia, angioedema, and serum sickness.
(d) Before penicillin therapy begins, the patient’s history should be evaluated for reactions to penicillin. A positive
history places the patient at heightened risk for a subsequent reaction. In most cases, such patients should receive a
substitute antibiotic. (However, hypersensitivity reactions may occur even in patients with a negative history.)
(2) Other adverse effects of natural penicillins include GI distress (e.g., nausea, diarrhea), bone marrow suppression
(e.g., impaired platelet aggregation, agranulocytosis), and superinfection. With high-dose therapy, seizures may
occur, particularly in patients with renal impairment
 2- Penicillinase-resistant penicillins
These penicillins are not hydrolyzed by staphylococcal penicillinases (B-lactamases).
These agents include methicillin, nafcillin, and the isoxazolyl penicillins—dicloxacillin and oxacillin
Spectrum of activity.
Because these penicillins resist penicillinases, they are active against staphylococci that produce these enzymes.
Therapeutic uses
(1) Penicillinase-resistant penicillins are used solely in staphylococcal infections resulting from organisms that resist
natural penicillins.
(2) These agents are less potent than natural penicillins against organisms susceptible to natural penicillins and thus
make poor substitutes in the treatment of infections caused by these organisms.
(3) Nafcillin is excreted by the liver and thus may be useful in treating staphylococcal infections in patients with renal
impairment.
(4) Oxacillin and dicloxacillin are most valuable in long-term therapy of serious staphylococcal infections (e.g.,
endocarditis, osteomyelitis) and in the treatment of minor staphylococcal infections of the skin and soft tissues.
Precautions and monitoring effects
(1) As with all penicillins, the penicillinase-resistant group can cause hypersensitivity reactions
(2) Methicillin may cause nephrotoxicity and interstitial nephritis.
(3) Oxacillin may be hepatotoxic.
(4) Complete cross-resistance exists among the penicillinase-resistant penicillins.
e. Significant interactions. Probenecid increases blood levels of these penicillins and may be given concurrently for
purpose

3- Aminopenicillins.
This penicillin group includes the semisynthetic agents ampicillin and amoxicillinBecause of their wider antibacterial spectrum,
these drugs are also known as broad-spectrum penicillins. .
Spectrum of activity.
Aminopenicillins have a spectrum that is similar to but broader than that of the natural and penicillinase-resistant penicillins.
Easily destroyed by staphylococcal penicillinases, aminopenicillins are ineffective against most staphylococcal organisms.
Against most bacteria sensitive to penicillin G, aminopenicillins are slightly less effective than this agent.
Therapeutic uses
Aminopenicillins are used to treat gonococcal infections, upper respiratory infections, uncomplicated urinary tract infections,
and otitis media caused by susceptible organisms.
(1) For infections resulting from penicillin-resistant organisms, ampicillin may be given in combination with sulbactam (Unasyn).
(2) Amoxicillin is less eff ective than ampicillin against shigellosis.
(3) Amoxicillin is more effective against S. aureus, Klebsiella, and Bacteroides fragilis infections when administered in
combination with clavulanic acid—amoxicillin/potassium clavulanate because clavulanic acid inactivates penicillinases.
Precautions and monitoring effects
(1) Hypersensitivity reactions may occur
(2) Diarrhea is most common with ampicillin.
(3) In addition to the urticarial hypersensitivity rash seen with all penicillins, ampicillin and amoxicillin frequently cause a
generalized erythematous, maculopapular rash. (This occurs in 5% to 10% of patients receiving ampicillin.)

4- Extended-spectrum penicillins.
These agents have the widest antibacterial spectrum of all penicillins. Also called antipseudomonal penicillins, this
group includes the carboxypenicillin (e.g., ticarcillin) and the ureidopenicillin (e.g., piperacillin ) .
Spectrum of activity
These drugs have a spectrum similar to that of the aminopenicillins but also are eff ective against Klebsiella and
Enterobacter spp., some B. fragilis organisms, and indole-positive Proteus and Pseudomonas organisms.
(1) Ticarcillin is active against P. aeruginosa. Combined with clavulanic acid (Timentin), ticarcillin has enhanced
activity against organisms that resist ticarcillin alone.
(2) Piperacillin is more active than ticarcillin against Pseudomonas organisms.
(3) Piperacillin and tazobactam. Tazobactam is a B-lactamase inhibitor that expands the spectrum of activity to
include some organisms not sensitive to piperacillin alone (if resistance is the result of B-lactamase production),
including strains of staphylococci, Haemophilus, Bacteroides, and Enterobacteriaceae. Generally, tazobactam does
not enhance activity against Pseudomonas.
Therapeutic uses
Extended-spectrum penicillins are used mainly to treat serious infections caused by gram-negative organisms (e.g.,
sepsis; pneumonia; infections of the abdomen, bone, and soft tissues). Piperacillin/tazobactam is effective in the
treatment of nosocomial pneumonia.
Precautions and monitoring effects
(1) Hypersensitivity reactions may occur
(2) Ticarcillin may cause hypokalemia.
(3) The high sodium content of ticarcillin may pose a danger to patients with heart failure (HF).
(4) All inhibit platelet aggregation, which may result in bleeding.