Cephalosporins Classification Question And Answers

 β-lactamase Inhibitors

Question 2. Write a short note on β – lactams inhibitors
Answer:

β – lactams inhibitors:

β-lactamases are enzymes produced by bacteria that open up the β-lactam ring and inactivate the β-lactam antibiotics. β-lactamase inhibitors (BLI)—clavulanate acid, sulbactam and tazobactam inactivate β-lactamases and prevent destruction of β-lactam antibiotics

• They broaden the antibacterial spectrum of penicillins to include penicillinase-producing staphylococci, gonococci, E. coli, H. influenzae and others.
• There are many types of β-lactamases and only some are inhibited by BLI.

Read And Learn More: Pharmacology Question And Answers

• Though clavulanic acid, sulbactam, and tazobactam are β-lactam compounds, they have no antibacterial activity.
• They are not effective against β-lactamases produced by Pseudomonas, Enterobacter and
• MRSA.
• Each BLI is combined with penicillin having a suitable pharmacokinetic profile.

Mind Map Of Β-Lactamase Inhibitors

Drugs And Route:

Though the above are the approved combinations, β-lactamase inhibitors with several other β-lactam antibiotics including cephalosporins are available for use.

Cephalosporins

• Cephalosporins derived from cephalosporin-C are semisynthetic antibiotics with a β-lactam ring.
• They have a wider spectrum of activity than penicillins.

Cephalosporins Classification:

• Mechanism of action: Cephalosporins are bactericidal and inhibit bacterial cell wall synthesis similar to penicillins.
• Resistance: As in the case of penicillins, beta-lactamases or cephalosporinases and altered target proteins, i.e. altered PBPs lead to resistance to cephalosporins.

Mind Map Of Cephalosporins:

Salient features of some Cephalosporins:

Cephalosporins Mechanism of action:

Cephalosporins are bactericidal and inhibit the bacterial cell wall synthesis similar to penicillins.

cephalosporins Resistance:

As in the case of penicillins, beta-lactamases or cephalosporinases and altered target proteins, i.e. altered PBPs lead to resistance to cephalosporins.

Mind Map Of Cephalosporins

Cephalosporins Adverse Reactions:

Cephalosporins are generally well-tolerated.

1. Hypersensitivity: Hypersensitivity reactions like skin rashes, fever, serum sickness and rarely anaphylaxis are seen. 20% of patients allergic to penicillins show cross-reactivity to cephalosporins. There are no reliable skin tests for testing allergies.
2. Nephrotoxicity: Mild nephrotoxicity is noted with some cephalosporins. Combination with other nephrotoxic drugs should be avoided.
3. Diarrhea: Diarrhea is More common with cefoperazone—could be because a large fraction of it is excreted through the bile.
4. Bleeding: Cephalosporins like cefoperazone, cefotetan, and cefamandole can cause bleeding due to hypoprothrombinemia and is more common in malnourished patients. This can be prevented by concurrent administration of vitamin K, 10 mg twice daily
5. A low WBC count may be seen though rarely.
6.  Pain at the injection site may occur.
7.  Disulfiram-like reactions with alcohol is reported with some cephalosporins, for example, Cefoperazone.

Cephalosporins Uses:

1. Gram-negative infections: Urinary, respiratory and soft tissue infections due to gram-negative organisms response—a third generation agent is used.
2. Surgical prophylaxis: Cefazolin is preferred due to its longer t½ and better tissue penetrability.
3. Gonorrhea: Ceftriaxone (single dose 250 mg) is the drug of choice.
4. Meningitis: Due to H.  influenzae, N. meningitidis, and S. pneumoniae – 3 generation cefotaxime or ceftriaxone may be used. Pseudomonas meningitis—ceftazidime + an aminoglycoside very effective.
5. Mixed aerobic–anaerobic infections: Common following pelvic surgeries—a third-generation agent is used.
6. Typhoid: As alternative to ciprofloxacin.
7.  Nosocomial infections:  Nosocomial infections can be treated with 3- generation cephalosporins.

Carbapenems

Carbapenems contain a β-lactam ring fused with a five-membered panel ring. Carbapenems include imipenem, meropenem, ertapenem, doripenem and faropenem.

Carbapenems Antibacterial spectrum:

Carbapenems have a wide antibacterial spectrum and inhibit various gram-positive, and gram-negative organisms and anaerobes including streptococci, staphylococci, enterococci, Listeria, Enterobacteriaceae (including cephalosporin-resistant ones), Pseudomonas and B. fragilis.

Carbapenems Mechanism of action:

Similar to penicillins carbapenems inhibit bacterial cell wall synthesis and are highly resistant to most beta-lactamases.

Carbapenems Imipenem:

• Is not absorbed orally → given IV (500 mg/6–8 hours);
• Has good tissue penetrability and attains good CSF levels.
• Imipenem is inactivated quickly by a dehydropeptidase in the renal tubules. Hence, it is always combined with cilastatin, an inhibitor of dehydropeptidase to prolong its plasma half-life.
• Carbapenems are excreted through the kidneys—the dose should be reduced in renal faliure.

Carbapenems Adverse effects:

• Include nausea, vomiting, diarrhea, and allergic reactions, especially in patients allergic to other β-lactam antibiotics.
• High doses can occasionally (1.5%) cause seizures.

Carbapenems Uses:

• Imipenem-cilastatin is used in UTI, respiratory, skin, bone, soft tissue, intra-abdominal and gynecological infections due to susceptible microorganisms that are resistant to other antibiotics.
• Particularly useful in infections with penicillin-resistant pneumococci and other nosocomial infections resistant to other antibiotics.
• With an aminoglycoside in Pseudomonas infections.
• Drug of choice in Enterobacter infections resistant to β-lactamases.

Meropenem

Advantages of meropenem over imipenem:

• Meropenem is not destroyed by renal dipeptidase hence cilastatin not required.
• The risk of seizures is less than with imipenem.
• Indications of meropenem are similar to imipenem.
• Dose: 0.5–2 g q 8 hours slow IV

Ertapenem: Ertapenem  is similar to meropenem except that:

• Not useful against P. aeruginosa.
• Longer-acting given once daily 1 g daily IM/IV.
• Since ertapenem is an irritant, IM inj. painful—hence combined with 1% lignocaine.

Doripenem:

• Doripenem has better activity against gram-negative aerobes than gram-positive ones.
• Dose: 500 mg q 8 hours slow infusion over 4 hours.

Faropenem:

• Faropenem is orally effective with good efficacy against both gram-positive and gram-negative organisms and some anaerobes.
• Adverse effects are nausea, diarrhea, and abdominal pain.

Meropenem Uses:

• Bacterial sinusitis, community-acquired pneumonia, and genitourinary infections. It is not available in many countries but is marketed in India.
• Dose: 100–300 mg.

Carbacephems

Loracarbef:

• Loracarbef is a carbacephem.
• It is a synthetic beta-lactam antibiotic with properties similar to second-generation cephalosporins (cefaclor) and is, therefore, included by some under second-generation cephalosporins.
• It is orally effective and is largely excreted by the kidneys.