Assignment on Antibiotics

Mezlocillin

Mezlocillin is a 4th generation penicillin antibiotic which kills certain bacteria that cause infection, or stops their growth. It treats many kinds of infections including those of the skin, blood, CNS, respiratory tract, sinuses, and urinary tract. It also treats gynecological infections in women. This drug is discontinued in the US.

Therapeutic Category :

Beta-lactam antibacterial: Penicillin with extended spectrum.

Chemical Name :

IUPAC Name :

(2S,5R,6R)-6-[(2R)-2-[(3-methanesulfonyl-2-oxoimidazolidine-1-carbonyl)amino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Generic Name :

(i) Mezlocillin Mezlocillina

(ii) Mezlocilline

(iii) Bay F 1353

(iv) Mezlocillin Sodium

Trade Name :

Mezlin

Brand Name :

Baypen (Bayer - ITALY, GERMANY, AUSTRIA, FRANCE, ISRAEL)

Baypen (Bayer - SPAIN)

Melocin (Curasan - GERMANY)

Mezlin (Bayer - USA)

Optocillin (Bayer – AUSTRIA, GERMANY)

Chemistry :

Formula : C21H25N5O8S2

Molecular Weight: 539

Indication :

Treatment of infections of-

lower respiratory tract, urinary tract, skin or skin structure; intra-abdominal infections; uncomplicated gonorrhea; gynecological infections; septicemia; streptococcal infections; severe infections; and Pseudomonas infections caused by

susceptible strains of specific microorganisms and prophylaxis.

Dosage form :

Injectable Solution

Dose :

- Powder for injection 1 g (as sodium; contains 1.85 mEq sodium/g)- Powder for injection 2 g (as sodium)- Powder for injection 3 g (as sodium)- Powder for injection 4 g (as sodium)- Powder for injection 20 g (as sodium)

Frequency :

Adults :

IM/IV 200 to 300 mg/kg/day in 4 to 6 divided doses. Usual doses are 3 g q 4 hr or 4 g q 6 hr. IM Doses should not exceed 2 g/injection.

Children (older than 1 mo to younger than 12 yr) :

IM/IV 50 mg/kg q 4 hr.

Newborns :

IV 75 mg/kg q 6 to 12 hr.

Half Life :

1.3 to 4.4 hours

Mechanism of action :

Exerts bactericidal activity via inhibition of bacterial cell wall synthesis by binding one or more of the penicillin binding proteins (PBPs). Exerts bacterial autolytic effect by inhibition of certain PBPs related to the activation of a bacterial autolytic process.

Pharmacokinetics :

Absorption :

T max is 0.5 to 1 hr (IM); C max is 35 to 45 mcg/mL (1g IM) and 254 mcg/mL (4 g IV).

Distribution :

Protein binding is 16% to 42% and Vd is 0.23 L/kg.

Metabolism :

Metabolism is 20% to 30% hepatic.

Elimination :

55% to 60% is excreted renally as unchanged. The t ½ is 0.8 to 1.1 hr. Mezlocillin is removed by hemodialysis.

Pharmacodynamics :

Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains of H. influenzae, Klebsiella species, Pseudomonas species, Proteus mirabilis, E. coli, Enterobacter species, Streptococcus faecelis, Peptococcus species, Peptostreptococcus species, Bacteriodes species (including B. fragilis), Morganella morganii, Serratia species, N. gonorrhoeae, P. vulgaris, and Providencia rettgeri.

Interaction :

Drug Interaction :

Demeclocycline - Possible antagonism of action. Doxycycline - Possible antagonism of action. Ethinyl Estradiol - This anti-infectious agent could decrease the effect of

the oral contraceptive.

Methotrexate - The penicillin increases the effect and toxicity of methotrexate

Minocycline - Possible antagonism of action.

Disease interaction :

(i) Renal Dysfunction :

Most beta-lactam antibiotics are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibiotics and their metabolites may be increased and the half-lives prolonged in patients with impaired renal function.

(ii) Colitis :

Pseudomembranous colitis has been reported with most antibacterial agents and may range in severity from mild to life-threatening, with an onset of up to two months following cessation of therapy.

(iii) Coagulation Abnormalities :

The use of extended-spectrum penicillin antibiotics has rarely been associated with coagulation abnormalities manifested as prolonged prothrombin and bleeding times, abnormal platelet aggregation, purpura, and clinical bleeding.

(iv) Hemodialysis :

Penicillin antibiotics (except for agents in the penicillinase-resistant class) are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Side effects :

(i) Central Nervous System- Lethargy, irritability, hallucinations, epilepsy, dizziness, fatigue, sleeplessness, hyperactivity and prolonged muscle relaxation.

(ii) Skin- Skin scar.

(iii) Eye and ENT- Itchy eyes.

(iv) Gastrointestinal- Nausea, vomiting, abdominal cramps, diarrhea, rectal bleeding, flatulence, inflammation of intestine and loss of appetite.

(v) Genitourinary- Inflammation of kidney, absence of urine, protein in urine, blood/pus in urine and elevated Blood Urea Nitrogen.

(vi) Liver- Jaundice and inflammation of liver.

(vii) Blood- Anemia, decreased/altered blood cell counts, bone marrow depression and prolonged bleeding.

(viii) Metabolic- Elevated liver enzyme levels and reduced mineral and uric acid level in blood.

(ix) Miscellaneous- Life threatening allergic reactions that may lead to death, vaginal inflammation, fever, pain at site of injection, blood clots, vein irritation/inflammation and compression of spinal nerve.

Contraindications :

Conditions :

Mono, Serious Kidney Problems, Clostridium Difficile Bacteria Related Colitis

Allergies :

Penicillins betalactams

Incompatibility :

Parenteral aminoglycosides may inactivate aminoglycosides in vitro; do not mix in same IV solution.

Storage/Stability :

After mixing the injection solution can be stored for 24 to 72 hours at room temperature; one to seven days in a refrigerator between 2 and 8 degrees C (36 and 46 degrees F); or up to twenty eight days when frozen at —12 degrees C (10 degrees F). Storage times depend on diluent used.

Packaging :

1g,5g,10g,50g,100g/bottle. 1kg/tin for trial order. 25kg/drum for commercial quantity.

Reference :

http://www.drugbank.ca

http://www.drugs.com

http://pubchem.ncbi.nlm.nih.gov/

Thank you