unit 10.4: beta-lactam - other drugs

Aztreonam

* Monobactam
* limited to **aerobic Gr(-) organisms**
* Resistant to beta-lactamases by some organisms
* Klebsiella, Pseudomonas, Serratia
* An **inhibitor** of __cell wall synthesis binding to PBP3__
* No activity against gram (+) and anaerobes
* **Synergistic** with aminoglycosides
* No cross-allergenicity with penicillin

renal tubular secretion

**Aztreonam**:

Eliminated via ___

prolonged

**Aztreonam**:

Half-life is ___ in renal failure

Carbapenems

* **Low susceptibility** to beta-lactamases
* Resistant to most β –lactamases, **ESBL** (extended-spectrum BL)
* Wide activity against Gram(+) cocci, Gram (-) rods, Anaerobes
* **Pseudomonal** infections
* Drug of choice for **Enterobacter**

renal (kidney)

**Carbapenems**:

Excretion

Imipenem

**Carbapenems**:

* Rapidly inactivated by **renal dehydropeptidases I**
* Partial cross-allergenicity with penicillins

**Cilastatin**

* Inhibitor of the enzyme
* Increases the half-life
* Inhibits formation of **nephrotoxic metabolites**

**Carbapenems**: ***Imipenem***

imipenem is combined with ___ which inhibits **dehydropeptidase enzymes** in renal tubules that inhibit imipenem

Meropenem

**c**ot metabolized by renal dehydropeptidases

* Less likely to cause **seizure**

Ertapenem

**Carbapenems**:

* Less active against pseudomonas
* IM injection causes pain and irritation

Clavulanic acid, Sulbactam, Tazobactam

* Used in fixed combination with certain **hydrolyzable penicillins**
* **Plasmid-encoded** beta-lactamases

Vancomycin

**Inhibitors of Cell Wall Synthesis:**

* Bactericidal Against **Gram-positive cocci and anaerobes**
* Isolated from the bacterium ***Amycolatopsis orientalis***
* Inhibits transglycosylation
* drug of choice for **methicillin-resistant S. aureus (MRSA)**

D-Ala-D-Ala terminal

**Inhibitors of Cell Wall Synthesis:** ***Vancomycin***

* Binds to the ___ of the nascent peptidoglycan pentapeptide side chain

Red Man Syndrome

**Inhibitors of Cell Wall Synthesis:** ***Vancomycin***

* **Rapid IV infusion** may cause diffuse blushing a syndrome known as ___

Teicoplanin

**Inhibitors of Cell Wall Synthesis:** ***Vancomycin***

Similar drug

Fosfomycin

**Inhibitors of Cell Wall Synthesis:**

* Prevents the **formation of N-acetylmuramic acid** which is essential in peptidoglycan chain formation
* Synergistic with **beta-lactam and quinolones** in specific infections

**decreased intracellular accumulation** of the drug

**Inhibitors of Cell Wall Synthesis:** ***Fosfomycin***

* Resistance occurs via ___

Antimetabolite inhibitor of **cytosolic enolpyruvate transferase**

**Inhibitors of Cell Wall Synthesis:** ***Fosfomycin***

* Inhibits addition of **phosphoenolpyruvate** to UDP-N-acetylglucosamine

kidney with urinary levels **exceeding the MICs for many urinary tract pathogens**

**Inhibitors of Cell Wall Synthesis:** ***Fosfomycin***

Excretion

uncomplicated cystitis (UTI)

**Inhibitors of Cell Wall Synthesis:** ***Fosfomycin***

Clinical Use

fluoroquinolones

**Inhibitors of Cell Wall Synthesis:** ***Fosfomycin***

Drug is **less effective** than the 7-day course of treatment with ___

Bacitracin

**Inhibitors of Cell Wall Synthesis:**

* **Peptide** antibiotic
* Interferes with a **late stage in cell wall synthesis** in gram (+) organisms
* Topical only
* highly nephrotoxic when administered systemically
* Tracy strain of Bacillus subtilis

lipid carrier that **transfers peptidoglycan subunits**

**Inhibitors of Cell Wall Synthesis:** ***Bacitracin***

* Inhibits cell wall formation by interfering with the ___ to the growing cell wall

Cycloserine

**Inhibitors of Cell Wall Synthesis:**

* **Antimetabolite**
* Used only in TB caused by **organisms resistant to first-line antituberculous drugs**
* Produced by **Streptomyces orchidaceous**

**D-alanine** (tetrapeptide cross linker)

**Inhibitors of Cell Wall Synthesis:** ***Cycloserine***

Inhibits incorporation of ___ into peptidoglycan pentapeptide by __inhibiting alanine racemase__, *which converts l-alanine to d-alanine, and d-alanyl-d-alanine ligase*

Daptomycin

**Inhibitors of Cell Wall Synthesis:**

* Lipopeptide
* vancomycin-resistant strains of enterococci and S aureus (VRE, VRSA)
* Fermentation product of **Streptomyces roseosporus**
* myopathy

Depolarization

**Inhibitors of Cell Wall Synthesis:** ***Daptomycin***

* ___ of the cell membrane with potassium efflux and rapid cell death

Pulmonary surfactant

**Inhibitors of Cell Wall Synthesis:** ***Daptomycin***

* ___ antagonizes daptomycin, and it should **not be used to treat pneumonia**