Cephalosporins

Are semisynthetic antibiotics : cephalosporium & streptomyces The different pharmacological, pharmacokinetic, & antibacterial properties of individual Cephalosporins result from substitution of various groups on the basic mol.

Classification of Cephalosporins into generation according to their antibacterial spectrum & stability to -lactamases into:

Antibacterial spectrum

1-First-generation Cephalosporins : have in vitro activity

against streptococci, methicillin-sensitive S. aureus & few gm-ve bacilli. (cefazolin, cephalexin)

2-Second-generation Cephalosporins :

have greater stability against -lactamases inactivation & posses broader spectrum of activity to include gm+ve cocci, gm-ve organism & anaerobes. (cefuroxime)

3-Third-generation {extended-spectrum} Cephalosporins: high degree of in vitro potency & -

lactamases stability & a broder spectrum of action against many common gm-ve bac. & anaerobes with good activity against streptococci. (cefixime) orally (Cefotaxime, ceftriaxone) parentrally

4- Fourth generation Cephalosporins: it has great

activity against several gm+ve & gm-ve organism. (cefepime) parentrally.

Clinical uses
1-First-generation Cephalosporins have activity against most of the bacterial pathogens that colonize skin & infect wounds. 2-Also first-generation Cephalosporins are useful in antimicrobial prophylaxis before surgery. 3-Second-generation Cephalosporins: used in treatment & prophylaxis of lower abdominal & gynecological infection 4-A broad spectrum of antibac. activity makes third-generation Cephalosporins important in the treatment of wide range of infection including : Pneumonia, Peritonitis & sepsis syndrome

Adverse effects
1-GIT disturbances [nausea, vomiting, diarrhea] 2-Alteration in blood clotting time [increase bleeding with administration of large doses] 3-Nephrotoxicity in the individuals with a preexisting renal disorder 4-Allergic manifestation

Other -lactam Antibiotics

A-Carbapenems Imipenem

Imipenem, meropenem, doripenem and ertapenem

: Its active against most gm+ve & gm-ve & anaerobic bacteria More active than third-generation cepha. against P.aeruginosa. E. faecium, and methicilin-resistant strain of staph. Resist hydrolysis by most -lactamases First choice for the empirical therapy of many polymicrobial pulmonary, intraabdominal, soft tissue infection.

S.E : renal failure may lead to seizures , nausea, vomiting and diarrhea

B-Monobactams Aztreonam :
has excellent activity against gm-ve organism {P.aeruginosa, enterobacteria} It lakes activity against gm+ve organism & anaerobes It is given I.V, I.M exc. In urine S.E : Relatively non toxic, but it may cause phebitis, skin rash & abnormal liver function test Low immunogenic potential , thus may offer a safe alternative for patients allergic to penicillin &/or cephalosporins

It is a mixture of polypeptide produced by Bacillus subtilis It prevent cell wall synthesis by binding to a lipid pyrophosphate carrier that transport cell wall precursors to the growing cell wall. It inhibit the dephosphorylation of this lipid carrier, a step essential to the carrier molecules ability to accept cell wall constituents for transport It inhibits gm+ve cocci, including S. aureus, streptococci, a few gm-ve organism & one anaerobe, Clostridium defficile

Bacitracin

Bacitracin antibiotic

Clinical uses
1-Its highly active against Staph., Stre., pyogen & C. difficile & its used in lab. to differentiating betw. Group A stre. & other stre. 2- Used in combination with other agents [neomycin & polymyxim B] topically in treatment of impetigo & other superficial skin infections Nephrotoxicity associated with parenteral use

Glycopeptides
Vancomycin
is a complex tricyclic glycopeptide antibiotic produced by streptomyces orientalis Inhibit the synthesis of cell wall phospholipids as well as peptidoglycan polymerization in a time-dependent fashion by binding to the D-Ala-D-Ala side chain of the precursor pentapeptide. Active against gm+ve, bacteriostatic against Staph., strep., & entercocci, effective against gm+ve rods, but not gm-ve rods, mycobactrium, fungi . Poorly absorbed from GIT

Clinical uses
1-For life-threatening antibiotic-associated colitis due to C. defficile or S. aureus. 2-Prophylactic in dental patients 3-Prostatic heart valves or implanted with devices

S.E : Ototoxicity ,fever, chills, maculopapular skin rash.

Glycopeptides
Teicoplanin
Very similar to Vancomycin in mechanism of action and antibacterial spectrum. Unlike vancomycin, it can be given I.M as well as I.V. Has a long half-life (45-70) hrs. permitting once-daily dosing.

Telavancin

Semisynthetic lipoglycopepide derived from Vancomycin Active virsus G+ve bacteria, including strains with reduced susceptibility to Vancomycin. It is approved for treatment of complicated skin and soft tissue infection. It teratogenic, so it is contraindication with pregnancy.

Daptomycin

Other cell wall - or membrane - active agent

Novel cyclic lipopeptide fermentation product of streptomyces roseosporus. It is active against vancomycin-resistant strains of enterococci and S aureus. Act by binding to bacterial cytoplasmic memb., induce rapid depolarization of the memb. thus disrupting memb. function and inhibiting intracellular synthesis of DNA, RNA and protein. It is bactericidal and bacterial killing is concentration dependent. Has limited activity to Gm+ve organisms. Pulmonary surfactants antagonizes Daptomycin, thus , it should never be used in the treatment of pneumonia. Most common side effect include: -Constipation -Myalgias -Insomnia -Increased hepatic transamination and creatine phosphokinases.