Beta Lactam Antibiotics

The antibacterial activity of beta lactam antibiotics ranges from narrow spectrum to wide spectrum.

Penicillins

The first to be discovered and most widely used of all the antibiotics. Sir Alexander Fleming first noted the action of the penicillium mould on Staphylococcus aureus in 1928 and 1940 Florey and Chain isolated the active substance and produced a life-saving antibiotic.

Mode of action

• Cell walls are composed of peptidoglycan and to form it, sugars and peptides need to be linked together by an enzyme called transpeptidase.
• Penicillin blocks the action of this enzyme so that when bacteria divide to make new cells, the walls do not form correctly. They break and the bacterial cell is killed.
• However, most S. aureus now produce penicillinase, so further modification of the basic penicillin structure has produced antibiotics that can withstand penicillinase and remain effective, e.g. methicillin.
• They penetrate into body tissues and fluids, except for the cerebrospinal fluid.
• They are excreted in high concentrations in the urine.

Classification

• Penicillin G and Congeners
  • Penicillin G
  • Penicillin V
  • Benzothiazine Penicillin G
  • Procaine Penicillin G
  • Procaine + Benzothiazine Penicillin G

• Beta Lactamase Resistant Penicillins
  • Methicillin
  • Nafcillin
  • Oxacillin
  • Cloxacillin
  • Dicloxacillin

• Extended-Spectrum Penicillins
  • Aminopenicillins
  • Ampicillin
  • Bacampicillin
  • Amoxicillin
  • Carboxypenicillins
  • Carbencillin indanyl
  • Ticarcillin
  • Ureidopenicillin
  • Mezlocillin
  • Piperacillin
  • Ampicillin
  • Bacampicillin
  • Amoxicillin

• Extended-Spectrum Penicillins Plus Beta lactamase inhibitors
  • Amoxicillin + Clavulnate
  • Ampicillin + Sublactam
  • Piperacillin + Tazobactam
  • Ticarcillin + Clavulnate
  • Dicloxacillin

Indications of use

Natural Penicillins

Penicillin G

Preparations

1. Sod. penicillin G injection: Benzyl Pen 0.5 , 1mU inj. 0.5-5I.M./I.V. 6-12hrly. Available as dry powder in vial to be dissolved in sterile water.
2. Procaine penicillin G injections : Procaine PenicillinG 0.5-1 MU dry powder in vial 0.5-1 MU I.M. 12-24 hrly as aqueous soln.
3. Benzathine penicillin G Penidure La, Longacillin, Pencom, 0.6, 1.2, 2.4 MU as dry powder in vial. 0.6- 2.4 MU I.M. every 2-4 weeks as aqueous suspension.
4. Fortified procaine penicillin G injection: fortified PP inj. 3+1 lac U vial. Contains 3lac unit procaine penicillin + 1lac unit Sod. penicillin G.

Adverse Effects

Hypersensitivity : Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients.

• Serious reactions that can occur are:
  • Diarrhaea that is watery or bloody.
  • Fever, chills, body aches, flu symptoms.
  • Easy bruising or bleeding, unusual weakness.
  • Urinating less than usual or not at all.
  • Severe skin rash, itching, or peeling.
  • Agitation, confusion, unusual thoughts or behaviour.
  • Seizure (black-out or convulsions).
• Less serious reactions that are more likely to occur, such as:
  • Nausea, vomiting, stomach pain.
  • Vaginal itching or discharge.
  • Headache.
  • Swollen, black, or "hairy" tongue.
  • Thrush (white patches inside your mouth or throat).

Local Irritancy and Direct Toxicity

• Pain at injection site, nausea on oral ingestion and thrombophlebitis on injected vein are related expressions of irritancy.
• Toxicity of the brain may be manifested as mental confusion, muscular twitchings, convulsions and coma, when large doses >20MU are injected bleeding is also noticed.

Penicillinase Resistant Penicillins

Generic Name: Cloxacillin

Brand Name : Klox 0.25, 0.5 g cap,125 mg/3g dry syr, 0.25. 0.5g inj.

Bioclox, Clocilin 0.25, 0.5 g cap; 0,25, 0.5 g/vial inj.

Adverse effects

• Gastrointestinal : Nausea, diarrhea, abdominal pain.
• Fever, seizure with extremely high doses and/ renal failure, rash (maculopapular to exfoliative), vomiting, pseudomembranous colitis, vaginitis, eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, anemia, hemolytic anemia, prolonged PT, hepatotoxicity, transient elevated LFTs, hematuria, interstitial nephritis, increased BUN/creatinine, serum sickness-like reactions, hypersensitivity.

Extended-Spectrum Penicillins Beta lactamase inhibitors

Generic Name: Ampicillin

Brand Name: Ampilin, Roscillin, Biocilin 250, 500 mg cap; 125, 250mg/5ml dry cypr; 100mg/ml peadiatric drops.

Indication

• Urinary tract infection: ampicillin is the drug of choice.
• Respiratory tract infection: including bronchitis, sinusitis, otitis media.
• It is the first line of treatment in Meningitis, Gonorrhoea.
• Septiceamias and mixed infections.
• Sub-acute bacterial endocarditis.
• Bacillary dysentry and cholecystitis.
• Typhoid fever.

Adverse effects

• Diarrhoea is frequent after oral administration of ampicillin due to alteration of the gut microbial flora.
• It produces rashes, especially in patients with AIDS, BE virus infections or lymphatic leukemia.
• Patients with history of immediate type of hypersensitivity with PnG should not be given ampicillin.

Generic Name: Amoxicillin

It is a close congener of ampicillin, similar in all aspects except that oral absorption is better, incidence of diarrhoea is low.

Brand Name: Amoxylin, Novamox, Synamox 250, 500 mg cap, 125mg/5ml dry syr. Amoxil ,Mox 250,500 mg caps; 125 mg/5ml dry syr; 250, 500mg/vial inj.

Carboxy Penicillins

Generic Name: Carbencillin

Brand Name: Carbelin 1g, 5g per vial inj

The important feature of this penicillin is its activity against Pseudomonas auruginosa and indole positive Proteus not inhibited by PnG or aminopenicillins.

High doses are known to cause bleeding by interfering with platelet function.

Ureidopenicillins

Generic Name: Piperacillin

Brand Name: Piparfen 1g, 2g vials; Pipracil 2g, 4g vials for inj; contains 2mEq Na+ per g.

It is mainly used in Neutropenic and immuno-compromised patients with serious gm-ve infection.

Beta-Lactamase inhibitors

Generic Name: Clavulanic acid

Mechanism of Action : It inhibits a wide variety of Beta lactamases produced by both gm+ve and gm-ve bacteria but has no action of its own.

Indication

Coamoxiclav is indicated for

• Skin and soft tissue infection, intra abdominal and gynaecological sepsis, urinary, biliary and respiratory tract infections and gonorrhoea.

Brand Name: Augmentin, Enhancin, Amonate: Amoxicillin 250mg + Clavulanic acid 125mg tab; 1-2 tab TDS.

Augmentin: Amoxicilin 1g + Clavulanic acid 0.2g vial and 0.5 g + 0.1g vial; inject 1 vial deep I.M. or I.V. 6-8hrly.

Adverse effects

Similar to amoxicillin.

Generic Name: Sulbactam

Semisynthetic Beta lactmase inhibitor. Brand Name:Sulbacin; Ampitum: Ampicillin 1g + sulbactam 0.5g per vial inj. Betamporal; Sulbacin 375mg tab.

Indication

• PPNG gonorrhoea, sulbactam per se inhibits N gonorrhoeae.
• Mixed aerobic and anaerobic infections, intra abdominal and gynaecological sepsis, urinary, biliary and respiratory tract infections.

Cephalosporines

These are group of semi-synthetic antibiotics derived from 'cephalosporin -C'. They are conventionally divided into 4 generations.

First generation

Second Generation

Third generation

Fourth Generation

Mechanism of Action

All cephalosporins are bactericidal and have action similar to action of penicilin. They inhibit the bacterial cell wall synthesis by binding to proteins different from those that penicillins bind.

Adverse effects

All cephalosporins exhibit common side effects.

• Pain after I.M. injection occurs with many. This is very severe with cephalothin .Thrombophlebitis can occur on injection.
• Diarrhoea, due to alteration of gut ecology.
• Hypersensitivity caused by cephalosporins is similar to penicillins. Rashes are more frequent, but anaphylaxis, angioedema, asthma, edema and urtricaria may also occur.
• Cephalosporins show certain grade of nephrotoxicity. It is the highest with cephaloridine. In a few cases it may be accentuated with previous renal disease.
• Bleeding occurs with cephalosporin.
• Neutropenia and thrombocytopenia have been reported with ceftazidime.

First generation

Generic Name: Cefazolin

Brand Name: Alcizon, Orizolin 0.25, 0.5 g, 1g per vial inj. Dose- 0.25g 8hrly (mild case). 1g 6hrly (severe case) I.M. or I.V.

Indication

• Cefazolin is mainly used to treat bacterial infections of the skin.
• It can also be used to treat moderately severe bacterial infections involving the lung, bone, joint, stomach, blood, heart valve and urinary tract.
• It is more active against Klebsiella and E.Coli.
• It is preferred cephalosporin in surgical prophylaxis.

Adverse effects

Side effects from cefazolin are not common

Generic Name:Cephalexin

Brand Name: Cephacilin 250, 500 mg cap, Sporidex, Cephaxin 250, 500 mg cap, 125mg/5ml dry syp.

Indication

Amongst the multitude of possible indications the following should be mentioned in particular:

• Meningitis in neonates, children and adults (except pseudomonas infections).
• Multiresistant Gram-negative infections, in particular caused by enterobacters.
• Gonorrhoea caused by ß-lactamase producing gonococci (single dose of 250 mg I.M.).
• Osteomyelitis caused by Staphylococcus aureus.
• Disseminated and persisting forms of Lyme disease.
• Dose: 0.25-1g 6-8hrly. (children: 25-200mg/kg/day).

Contraindication

Cephalosporin hypersensitivity.

Adverse effects

• Pain induration and tenderness at injection site area.
• May develop hematological changes (eosinophilia, thrombocytosis, less frequently leucopenia).
• Diarrhoea,less frequently reported were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment.

Generic Name: Cephadrine

Brand Name: Ceflad 0.25, 0.5. 1g per vial inj.

Generic Name: Cefadroxil

Brand Name: Droxyl 0.5, 1g tab, 250mg/5ml sypr., Cefadrox 0.5 g cap,125mg/5ml sypr, 250 mg kid tab.

Second generation

Generic Name:Cefuroxime

Brand Name: Cefogen, Supacef, Furoxil 250 mg and 750mg/vial inj, 0.75- 1.5 g I.M. or I.V.8hrly.

Generic Name: Cefuroxime Axetil

Brand Name: Ceftum, Spizef 125, 250, 500 mg cap tab and 125mg/5ml susp.

Generic Name: Cefaclor

Brand Name: Keflor, Vercef, Distaclor 250 mg cap, 125 and 250 mg Distab, 125mg/5mldry syr, 50mg/mlped drops.

Third generation

Generic Name: Cefotaxime

Brand Name: Omnatax, Oritaxim, Claforan 0.25, 0.5, 1.0 gm per vial inj.

Indication

• Prominent indication in meningitis caused by gram negative bacteria.
• Hospital acquired infection.
• Septiceamia and infection in immuno-compromised patients.
• Dose: 1-2gm I.M. or I.V. 6-12 hly.

Generic Name: Ceftizoxime

Brand Name: Cefizox, Epocelin 0.5 -1g per vial inj.

Indication: similar to cefotaxime

Generic Name: Ceftriaxone

Brand Name: Oframax, Monocef , Monotax 0.25, 0.5, 1.0 g per vial inj.

Dose:1-2g I.V. or I.M. per day.

Indication

• Bacterial meningitis.
• Multi-resistant typhoid fever.
• Urinary tract infection.
• Abdominal sepsis and septiceamia.

Adverse effects

Hypoprothrombinemia and bleeding are specific adverse effects.

Generic Name: Ceftazidime

Brand Name: Fortum, Cefezid, Orzid 0.25, 0.5, 1.0 g per vial inj.

Indication

It is specifically used in febrile neutropenic patients with heamatological malignancies.

Adverse effects

Neutropenia & thrombocytopenia, rise in plasma transaminases and blood urea levels may be seen.

Generic Name: Cefaperazone

Brand Name: Magnamycin 0.25g, 1,2g inj ; Cefomycin, Nagaplus 1g inj; 1-2g I.M./I.V.12hrly.

Generic Name: Cefexime

Brand Name: Topcef, Orfix 100, 200 mg tab /cap. Cefspan 100 mg cap, 100mg/5ml syr.

Generic Name: Cefpodoxime proxetil

Brand Name: Cefoprox 100, 200 mg tab ,100mg/5ml dry syr; Cepodem 100, 200 mg tab, 50mg/5ml susp.

Generic Name: Cefdinir

Brand Name: Sefdin, Adcef 300mg cap, 125mg/5ml susp.

Generic Name: Cefbuten

Brand Name: Procadax 400 mg cap, 90mg/5ml powder for oral susp.

Fourth generation

Generic Name: Cefepime

Brand Name: Kefage 0.5, 1.0g inj.

Generic Name: Cefpirome

Brand Name: Cefrom, Ceforth 1g inj.

Carbapenems, Monobactams, Carbacephems

Carbapenems

Generic Name: Imipenem

Is an extremely potent and very broad spectrum beta lactam antibiotic whose range of activities includes gram positive cocci, enterobacteriaceae, Ps. aeuroginosa, Listeria as well as anaerobes.

Indication

• It is commonly used in serious hospital acquired infections especially in cancer, AIDS and neutropenic infections.

Adverse Effects

• Imipenem has the intensity to induce seizures in high doses.

Monobactams

Generic Name: Aztreonam

It inhibits gram negative enteric bacilli and H.influenzae at low concentrations and Pseudomonas at moderate concentration.

Indication

• It is commonly used in serious hospital acquired infections originating from urinary, biliary, gastroitestinal and female genital tract.

Carbacephems

Generic Name: Loracarbef

The carbacephems are a new class of beta-lactam antibiotics that are similar in structure to the cephalosporins. Carbacephems differ from cephalosporins, however, in the substitution of a sulphur atom in the dihydrothiazine ring with a methylene group to form a tetrahydropyridine ring. The result of this structural difference is the carbacephem class.

Indication

• Loracarbef is indicated in the treatment of patients with mild to moderate infections caused by susceptible strains of microorganisms such as S. pneumoniae, H. influenzae (including b-lactamase-producing strains), M. catarrhalis, S. pyogenes, E.coli or S. saprophyticus in conditions like lower and upper respiratory tract, pharyngitis, tonsillitis, acute exacerbation of chronic bronchitis, urinary tract infections.

Adverse Effects

• All Patients
  • Gastrointestinal: The most commonly observed adverse reactions were related to the gastrointestinal system. The incidence of gastrointestinal adverse reactions increased in patients treated with higher doses. Individual event rates included diarrhaea 4.1% ;nausea 1.9%; vomiting 1.4%; abdominal pain 1.4% and anorexia.
  • Hypersensitivity: Hypersensitivity reactions include, skin rashes, utricaria and pruritis.
  • Central nervous system: Headache, dizziness and somnolence.
  • Heamatologi and lymphatic systems: Transient thrombocytopenia, leukopenia and eosinophilia.
  • Cardiovascular system: Vasodilatation.