Cephalosporins

What fungus, isolated in 1948 by Brotzu, was the original source of cephalosporins?

Cephalosporium acremonium.

Crude filtrates from Cephalosporium acremonium cultures were found to inhibit the in vitro growth of which bacterium?

S. aureus (Staphylococcus aureus).

What were the names of the three distinct antibiotics found in the culture fluids of the Sardinian fungus?

Cephalosporin P, N, and C.

What is the name of the active nucleus isolated from cephalosporin C?

7-aminocephalosporanic acid.

The chemical structure of Cephalosporin C contains a side chain derived from _____ acid.

D-α-aminoadipic acid.

Modifications at which position of the cephalosporin β-lactam ring alter antibacterial activity?

Position 7.

Substitutions at which position of the dihydrothiazine ring in cephalosporins are associated with changes in metabolism and pharmacokinetics?

Position 3.

How does the mechanism of action (MOA) of cephalosporins compare to that of penicillins?

The MOA is similar, but cephalosporins are more stable to β-lactamase, giving them a broader spectrum of activity.

Name two orally absorbed cephalosporins mentioned in the text.

Any two of: cephalexin, cephradine, cefaclor, cefuroxime axetil, cefixime.

Which two 3rd-generation cephalosporins penetrate the cerebrospinal fluid and are useful in meningitis?

Ceftriaxone and ceftizoxime (also 2nd gen Cefuroxime and 3rd gen Cefotaxime).

Which cephalosporin is found in high concentrations in the bile?

Cefoperazone.

How are most cephalosporins excreted, and what adjustment is needed for patients with renal insufficiency?

They are excreted through the kidneys, so dosage should be adjusted.

Which two cephalosporins are exceptions to renal excretion and are predominantly excreted in the bile?

Cefpiramide and cefoperazone.

Which 1st-generation cephalosporin is parenteral and considered the drug of choice for single-injection surgical prophylaxis?

Cefazolin.

First-generation cephalosporins have good activity against gram-positive cocci but are not effective against which two specific types?

Enterococci and MRSA (methicillin-resistant S. aureus).

For colorectal surgery prophylaxis, which 2nd-generation cephalosporin is preferred over the 1st-generation Cefazolin?

Cefoxitin.

Cefoxitin and cefotetan are technically classified as what type of antibiotic, though grouped with cephalosporins?

Cephamycins.

How do cephamycins structurally differ from cephalosporins?

They have a methoxy group at position 7 of the β-lactam ring of the 7-aminocephalosporanic acid nucleus.

The cephamycins (e.g., cefoxitin, cefotetan) are notably active against which group of anaerobic bacteria?

Bacteroides sp., including B. fragilis.

Which two 3rd-generation cephalosporins are active against Pseudomonas aeruginosa?

Ceftazidime and cefoperazone

The oral 3rd-generation cephalosporins cefixime and ceftibuten have little activity against which gram-positive bacterium?

S. aureus (Staphylococcus aureus).

How does the activity of 4th-generation cephalosporins against gram-negative bacilli compare to 3rd-generation drugs?

They have enhanced activity, including against ESBL-producing and ampC β-lactamase-producing Enterobacteriaceae.

The 4th-generation cephalosporin _____ has activity against P. aeruginosa similar to ceftazidime.

Cefepime.

Which 5th-generation cephalosporin is active against Methicillin-resistant S. aureus (MRSA)?

Ceftobiprole.

What is a primary initial indication for the 5th-generation cephalosporin, ceftobiprole?

Complicated skin infections such as diabetic foot.

What is the estimated frequency of cross-allergenicity between penicillins and cephalosporins?

Approximately 5-10%.

Under what condition should patients with a penicillin allergy not receive cephalosporins?

If they have a history of anaphylaxis to penicillins.

Cephalosporins containing a _____ group frequently cause hypoprothrombinemia and disulfiram-like reactions with alcohol.

methylthiotetrazole

What can be administered to prevent bleeding disorders caused by cephalosporins with a methylthiotetrazole group?

Vitamin K.

One mechanism of bacterial resistance to cephalosporins involves enzymes called _____ that hydrolyze the drug's ring structure.

β-lactamases.

How do carbapenems compare to other β-lactam antibiotics in terms of their spectrum of activity?

They have the broadest spectrum of activity.

Why is Imipenem administered with Cilastatin?

Cilastatin inhibits renal dipeptidase, preventing the breakdown of Imipenem into a nephrotoxic metabolite.

Imipenem is a broad-spectrum carbapenem but is not effective against which three mentioned organisms/strains?

Enterococcus faecium, MRSA, and Clostridium.

A major adverse reaction of carbapenems, especially at high concentrations or in patients with renal insufficiency, is _____.

Seizures.

Which carbapenem does not require co-administration with cilastatin and has a lower incidence of seizures than imipenem?

Meropenem.

Which carbapenem has a long half-life of 4 hours, allowing for once or twice daily dosing?

Ertapenem.

What is the structural classification of Aztreonam?

It is a monocyclic β-lactam, or a monobactam.

Aztreonam is active against gram-negative rods, including which two organisms mentioned in the text?

Pseudomonas and Serratia.

What is the key advantage of Aztreonam regarding allergies?

Patients allergic to other β-lactam antibiotics (like penicillin) do not typically show cross-sensitivity.

What is the spectrum of activity for Vancomycin?

It is effective only against gram-positive organisms.

What is Vancomycin's mechanism of action?

It inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide.

How have enterococci developed resistance to Vancomycin?

By modifying the binding site where the terminal D-Ala is replaced by D-lactate.

Vancomycin is synergistic in vitro with gentamicin against which specific enterococcus strains?

Enterococcus faecium and Enterococcus faecalis (if they do not have high-level aminoglycoside resistance).

When is vancomycin administered orally?

Only for the treatment of enterocolitis caused by C. difficile.

What is the main indication for intravenous Vancomycin?

Sepsis or endocarditis caused by methicillin-resistant staphylococci (MRSA).

What infusion-related reaction is commonly associated with Vancomycin?

"Red man" or "red neck" syndrome, caused by histamine release.

How can "red man" syndrome be prevented when administering Vancomycin?

By prolonging the infusion period to 1-2 hours or increasing the dosing interval.

Administration of vancomycin with an _____ increases the risk of ototoxicity and nephrotoxicity.

aminoglycoside.

What is the mechanism of action for Bacitracin?

It inhibits cell wall formation by interfering with peptidoglycan transfer to the developing cell wall.

Why is the use of Bacitracin limited to topical applications?

Due to its significant nephrotoxicity with systemic administration.

Cycloserine, a structural analog of _____, is used almost exclusively for treating tuberculosis.

D-alanine.

What type of adverse effects are associated with Cycloserine at higher than clinical doses?

CNS toxicity.

What class of antibiotics are described as amphipathic basic peptides that disrupt bacterial cell membranes?

Polymixins.

Polymixins are active against gram-negative bacteria but which two mentioned gram-negative genera are resistant?

Proteus and Neisseria.

What is a major clinical use for topical Polymixin B sulfate?

Treatment of external otitis and corneal ulcers due to Pseudomonas aeruginosa.