Antimicrobial preparations / Penicillin group
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Penicillin group

Penicillins are the first class of antibacterial medications developed on basis of biologically active substances produced by certain microorganisms. The first penicillins benzylpenicillin was obtained at the beginning of 1940 years.

Penicillins belong to a group of antibiotics called β-lactams (beta-lactams) which also include cephalosporin, carbapenems, monobactams. The similarity of chemical structure predetermine similar action mechanism of all β-lactam namely interfering with synthesis of bacterial cell wall.
Taking into account high clinical effectiveness and low toxicity, β-lactam lactam antibiotics form the bases of antimicrobial chemotherapy and occupy the leading role in the treatment of the majority infections.
Currently the group of penicillins includes more than 20 antibiotics which are divided into several categories:
1.Natural Penicillins (Penicillin G, Procaine, Penicillin G, Penicillin V, Benzathine) The natural penicillins were the first antibiotics introduced in clinical practice. Natural antibiotics are active against gram-positive bacteria such as Streptococcus spp, Staphylococcus spp., Bacillus spp., in less degree against Enterococcus spp.
L.monocytogenes, E.rhusiopathiae and corynebacteria (including C.diphtheriae), the most of anaerobic bacteria (Peptostreptococcus spp., Clostridium spp.) are highly sensitive to natural penicillins. Natural penicillins are highly effective against spirochetes (Treponema, Borrelia, Leptospira).
2.Penicillinase-Resistant Penicillins (Cloxacillin, Dicloxacillin, Methicillin, Nafcillin, Oxacillin). Methicillin was the first member of this group, followed by oxacillin, nafcillin, cloxacillin and dicloxacillin. Currently Oxacillin is the most widespread among penicillinase-resistant penicillins and is actively used for the treatment of infections caused by staphylococci including PRSA.
3.Aminopenicillins (Ampicillin, Amoxicillin, Bacampicillin). Aminopenicillins were the first penicillins discovered to be active against gram-negative bacteria (such as E. coli and H. influenzae). Aminopenicillins are acid-resistant and that is why are administered orally. Aminopenicillins possess a broader spectrum of antibacterial activity against some strains such as E.coli, Shigella spp., Salmonella spp. and P.mirabilis, which are characterized by low levels of production of chromosomal β-lactamase. Aminopenicillins are susceptible to hydrolysis by beta-lactamses and that is why are usually come in combination with beta-lactamse inhibitors.
4.Extended Spectrum Penicillins (sometimes called anti-pseudomonal penicillins). Extended spectrum penicillins include both alpha-carboxypenicillins (carbenicillin and ticarcillin) and acylaminopenicillins (piperacillin, azlocillin, and mezlocillin). These antibiotics possess similar spectrum of antibacterial activity as aminopenicillins but with additional bactericidal activity against the majority of gram negative microorganisms such as Pseudomonas aeruginosa. Along with aminopenicillins, extended spectrum penicillins are inactivated by beta-lactamase. These drugs can be used in monotherapy of infectious diseases or in combination with aminoglycosides.

Action mechanism
All beta-lactam antibiotics exert bactericidal action which is associated with inhibition of bacterial cell wall production. Their target is penicillin-depending bacterial proteins which fulfill a function of enzymes on the final stage of peptidoglycan synthesis-biopolymer and the main component of bacterial cell wall. Suppressing of peptidoglycan synthesis leads to consecutive bacterial lysis. Some of penicillin antibiotic exert bacteriostatic effect in low doses which may or may not control the infection

Penicillins indication
The indications for penicillins vary depending on penicillins group. Natural penicillins are used in:

Infections caused by S.pyogenes, and their consequences:

  • tonsillopharyngitis
  • scarlet fever
  • erysipelas
  • year-round rheumatism prevention.

Infections caused by S.pneumoniae:

  • community-acquired pneumonia
  • meningitis
  • sepsis
  • prophylaxis of pneumococcal infections after splenectomy.

Infections caused by other streptococci:

  • Infective endocarditis (in combination with gentamicin or streptomycin);
  • Meningococcal infections (meningitis)
  • Syphilis
  • Leptospirosis
  • Tick-borne borreliosis (Lyme disease)
  • Gangrenous emphysema
  • Actinomycosis

Penicillinase-Resistant Penicillins and namely oxacillin is used in:

  • Staphylococcal infections of different localizations and susceptible to oxacillin
  • Infections of skin, soft tissue, bone and joints
  • Pneumonia
  • Infectious endocarditis
  • Meningitis
  • Sepsis

Aminopenicillins are indicated for the treatment of:

  • Infections of upper and lower respiratory system including sinusitis, aggravation of chronic bronchitis, pneumonia
  • Urinary tract infections: cystitis, pyelonephritis
  • Meningitis caused by H.influenzae and L.monocytogenes
  • Endocarditis
  • Intestinal infections caused by shigella and salmonella (ampicillin)
  • Eradication of H.pylori in patients with stomach and duodenal ulcers
  • Prophylaxisof endocarditis
  • Intraabdominal infections
  • Skin and soft tissue infections

Carboxypenicillins are usually indicated for the treatment of:
Nosocomial infections caused by sensitive strains P.aeruginosa. Carboxypenicillins must be used only in combination with other antibacterial preparations (aminoglycosides, fluorquinolones). Ticarcillin in combination with clavulonate is indicated in:

  • Lower respiratory tract infections
  • Urinary tract infections
  • Intraabdominal infections
  • Sepsis
  • Infections of skin, soft tissue, bones and joints

Ureidopenicillins usually come in combination with aminoglycosides and are used in the treatment of infections caused by P.aeruginosa
Some of the ureidopenicillis are used against:

  • Lower respiratory tract infections such as nosocomial pneumonia, pleural empyema, pulmonary abscess
  • Skin and soft tissue infection including diabetic foot
  • Intraabdominal infections
  • Infections of the gall bladder and bile passages
  • Urinary tract infections

Penicillins contraindication. General contraindications include:

  • Known reactions of hypersensitivity to all beta-lactam antibiotics
  • Severe liver diseases
  • Severe kidney diseases
  • Pregnancy
  • Breastfeeding

Penicillins side effects. Penicillin are considered safe and well-tolerable preparations. The most common side effects include:

  • Allergic reactions: urticaria, skin rash, Quincke's edema, fever, eosinophilia, bronchospasm, anaphylactic shock (often using benzylpenicillin). In case of anaphylactic shock medical first aid should be carried: intubation (if necessarily), oxygenation, adrenaline, corticosteroids
  • CNS: headache, tremors, convulsions (often in children and in patients with renal failure caused by Carbenicillin or very high doses of benzylpenicillin), mental disorders (with high doses of benzylpenicillin procaine)
  • Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, pseudomembranous colitis (in most cases using ampicillin and aminopenicillins with beta-lactamase inhibitors)
  • Metabolism: high potassium blood levels (when using high doses of benzylpenicillin potassium salt in patients with renal insufficiency, as well as its combination with potassium-sparing diuretics, potassium preparations, or ACE inhibitors), hypernatremia (especially common for carbenicillin, rarely for ureidopenicillins and high doses of benzylpenicillin sodium salt), which may be accompanied by edema (patients with congestive heart failure), elevated blood pressure
  • Local reactions: pain and infiltration at injection site, phlebitis
  • Liver: increased activity of transaminases accompanied by fever, nausea, vomiting (especially common for oxacillin)
  • Hematologic reactions: reduction of hemoglobin levels, neutropenia (usually using oxacillin); disorders of platelet aggregation, sometimes with thrombocytopenia (using Carbenicillin, in rare cases - ureidopenicillins)
  • Kidneys: transient hematuria in children (often using oxacillin), interstitial nephritis (very rare)
  • Vascular complications (caused by procaine benzylpenicillin and benzathine benzylpenicillin): - ischemia and gangrene of the extremities caused intraarterial injection; Nicolau syndrome - pulmonary and cerebral embolism during
  • Other: skin rash accompanied by itching, oral candidiasis

Drug interactions
Penicillin should not be mixed in one vial with other antibiotics.
There is an increased risk of skin rash in concomitant application with allopurinol.
Potassium-sparing diuretics, ACE inhibitors may increase the risk of hyperpotassemia.
Penicillins should be used with caution in combination with blood thinners and antiplatelets.
Bile-acid sequestrants may bind penicillins in the digestive system and thus decrease their bioavailability.
Oral penicillins may decrease the effectiveness of oral birth control pills.
Penicillin are able to impair the elimination of methotrexate due inhibiting of tubular secretion.