Third Generation Cephalosporins 

Prototype drugs are CEFOTAXIME (IV) and CEFIXIME (oral). CEFTAZIDIME (for Pseudomonas aeruginosa.).

Further expansion of Gm negative spectrum to include hard to treat organisms such as Enterobacter, Serratia, and Pseudomonas. 
In addition to better Gm negative spectrum, this group has improved pharmacokinetic properties (longer half-lives) that allow once daily dosing with some agents. In general, activity toward Gm + bacteria is reduced. These are specialty antibiotics that should be reserved for specific uses. 

Enterobacteriaciae that are almost always sensitive (>95% sensitive)
E. coli
Proteus mirabilis (indole –)
Proteus vulgaris (indole +)
Klebsiella pneumoniae

Gram negative bacilli that are generally sensitive (>75% sensitive)
Morganella morganii
Providencia retgerri
Citrobacter freundii
Serratia marcescens
Pseudomonas aeruginosa (Ceftazidime only)

Gram negative bacilli that are sometimes sensitive (<75% sensitive)
Enterobacter
Stenotrophomonas (Xanthomonas) maltophilia (Cefoperazone & Ceftazidime only)
Acinetobacter

--> cefepime & cefpirome are promising for these bacteria

Bacteria that are resistant
Listeria monocytogenes
Pseudomonas cepacia
Enterococcus sp. 

Uses
1. Gram negative septicemia & other serious Gm – infections
2. Pseudomonas aeruginosa infections (Ceftazidime - 90% effective)
3. Gram negative meningitis - Cefotaxime, Ceftriaxone, Cefepime. For empiric therapy add vancomycin ± rifampin to cover resistant Strep. pneumoniae
4. Gonorrhea - Single shot of Ceftriaxone is drug of choice. Oral cefixime and ceftibuten are also OK.
5. Complicated urinary tract infections, pyelonephritis
6. Osteomyelitis - Ceftriaxone in home health care situations
7. Lyme disease - ceftriaxone in home health care situations

Ampicillin offered a broader spectrum of activity than either of the original penicillins and allowed doctors to treat a broader range of both Gram-positive and Gram-negative infections. Ampicillin is often used in molecular biology as a test for the uptake of genes (e.g., by plasmids) by bacteria (e.g., E. coli)

Distribution

Three major controlling factors:  

Blood Flow to Tissues:  rarely a limiting factor, except in cases of abscesses and tumors.
Exiting the Vascular System:  Occurs at capillary beds.
- Typical Capillary Beds - drugs pass between cells 
- The Blood-Brain Barrier-  Tight junctions here, so drugs must pass through cells.  Must then be lipid soluble, or have transport system.
- Placenta - Does not constitute an absolute barrier to passage of drugs.  Lipid soluble, nonionized compounds readily pass.  
- Protein Binding:  Albumin is most important plasma protein in this respect.  It always remains in the blood stream, so drugs that are highly protein bound are not free to leave the bloodstream.  Restricts the distribution of drugs, and can be source of drug interactions.

Entering Cells:  some drugs must enter cells to reach sites of action.

Clavulanic acid is often combined with amoxicillin to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. It works by preventing bacterium that release beta-lactamases from destroying amoxicillin.

Propoxyphene

• A methadone analog.Used orally to relieve mild to moderate pain.
• A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
• Cannot be used parenterally because of irritant properties.
• Has a low addiction potential primarily due to its lack of potency as an opiate.
• The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
• Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
• CNS depression is additive with other CNS depressants.

Clarithromycin Used to treat  pharyngitis, tonsillitis, acute maxillary

sinusitis, acute bacterial exacerbation of chronic  bronchitis,  pneumonia (especially atypical pneumonias associated with Chlamydia pneumoniae or TWAR), skin and skin structure infections, and, in HIV and AIDS patients to prevent, and to treat, disseminated Mycobacterium avium complex or MAC.

Unlike erythromycin, clarithromycin is acid-stable and can therefore be taken orally without being protected from gastric acids. It is readily absorbed, and diffused into most tissues and phagocytes.

Clarithromycin has a fairly rapid first-pass hepatic metabolism, i.e it is metabolised by the liver. However, this metabolite, 14-hydroxy clarithromycin is almost twice as active as clarithromycin.

Contraindications Clarithromycin should be used with caution if the patient has liver or kidney disease, certain heart problems (e.g., QTc prolongation or bradycardia), or a mineral imbalance (e.g., low potassium or magnesium levels).