Saturday, March 1, 2014

Four Generations of Cephalosporins

Hello! This is the outline on four generations of cephalosporins created by Shannon Finucane, Miriah Gilmore, and Natalia Fortygin. Please let us know if we need to correct anything or if we omitted any important information. Your input is greatly appreciated!

Cephalosporins
            -discovered in Sardinia, 1948
            -1960’s Cephalosporins used clinically
            -fungus called Cephalosporium acremonium
           
Cephalosporin Structure and Function
            -Beta-lactum structure
            -inhibits the bacterial enzyme needed for well wall synthesis
            -Bactericidal: bacterial cell lysis and death result

Cephalosporin Generations
            -Four groups (or generations) currently used
            -Each generation is effective against a broader spectrum of bacteria
            -Generations 3 & 4, and some of generation 2 are resistant to beta-lactamase (enzyme that breaks down PCN)

First-Generation Cephalosporins
            -cefadroxil (Duricef)
                        -Availability: PO (1-2 g/d in 1-2 divided doses)
                        -Tx of (or Indication): UTI, beta hemolytic strep, staph skin infections
            -cefazolin sodium (Ancef)
                        -Availability: IV/IM (250mg-2g q6-8h), PO (250-500mg q8h)
                        -Tx of: infections (respiratory, urinary, skin, bone, joint, genitals) and                                                         endocarditis
            -cepalexin (Keflex)
                        -Availability: PO (250-500mg q6h)
                        -Tx of: infections of otitis media, skin, bone, respiratory and urinary tract
            -cephradine (Velosef)
                        -Availability: PO (250-500mg q6h, or 500mg-1g q12h)
                        -Tx of: similar to cephalexin

Second-Generation Cephalosporins
            -cefaclor (Ceclor, Ranoclor)
                        -Availabilty: PO (250-500mg q8h)
                        -Tx of: infections of respiratory, urinary, skin, ear, ampicillin-resistant 
                         strains and certain gram-negative organisms
        
            -cefotetan (Cefotan)
                        -Availability: IM, IV (500mg-2g q12h)
                        -Tx of: gram-negative organisms
            -cefoxitin sodium (Mefoxin)
                        -Availability: IV (1-2g q6-8h)
                        -Tx of: severe infections, septicemia,
            -cefprozil monohydrate (Cefzil)
                        -Availability: PO (250-500 mg daily or q12h)
                        -Tx of: gram-positive bacilli
            -cefuroxime (Ceftin, Zinacef)
                        -Avail: PO (25-500mg q12h), IV/IM ( 750mg-1.5g q8h)
                        -Tx: meningitis, septicemia, cardiothoracic procedures, and surgical prophylaxis

Third-Generation Cephalosporins
            -cefdinir (Omnicef)
                        -Avail: PO (300mg q12h or 600mg daily)
                        -Tx: otitis media, acute sinusitis, chronic bronchitis, pharyngitis/tonsillitis, PNA,                           and skin infections
            -cefixime (Suprax)
                        -Avail: PO (400mg/d in 1-2 divided doses)
                        -Tx: UTI, otitis media, bronchitis, select strep, and gram-negative bacilli
            -cefoperazone (Cefobid)
                        -Avail: IM/IV (1-2g/12h)
                        -Tx: infections of respiratory and urinary tract, female genital tract,
            -cefotaxime (Claforan)
                        -Avail: IM/IV (1-2g q8-12h)
                        -Tx: P. aeruginosa, gram-negative meningitis
            -cefpodoxime (Vantin)
                        -Avail: PO (200mg q12h for10d)
                        -Tx: otitis media, respiratory and urinary tract infections
            -ceftazidime (Fortaz)
                        - Avail: PO (1-2g q8-12h)
                        -Tx: Pseudomanas spp.
            -ceftriaxone (Rocephin)
                        -Avail: IM/IV (1-2g/d)
                        -Tx: Similar to ceftizomine and cefotaxime
            -ceftizoxime sodium (Cefizox)
                        -Avail: PO (500mg-2g q8-12h)
                        -Tx: respiratory, urinary tract, skin, bone, joint infection, and surgical prophylaxis
            -ceftibuten (Cedax)
                        -Avail: PO (400mg/d for 10d)
                        -Tx: chronic bronchitis, pharyngitis, tonsillitis, gram-positive and negative                                      bacteria
            -cefditoren pivoxil (Spectracef)
                        -Avail: PO (200-400mg twice daily for 10d)
                        -Tx: chronic bronchitis, pharyngitis, tonsillitis, skin infections
Fourth-Generation Cephalosporins
            -cefepime (Maxipime)
                        -Avail: IV (0.5-1g q12h, in severe cases 2g q12h for 10d)
                        -Tx: similar to third-generation cephalosporins. Resistant to most beta-lactamase                           bacteria

Side Effects and Adverse Reactions to Cephalosporins
            -GI disturbances (nausea, vomiting, diarrhea)
            -alterations in blood clotting time (increased bleeding)
            -Nephrotoxicity: damage to kidneys with large doses and/or preexisting renal issues

Drug Interactions with Cephalosporins
            -Cephalosporins (Ceffamandole or Cefoperazone) + Alcohol
                        -can cause flushing, HA, N/V, muscular cramps
            -Cephalosporins + Uricosuric drugs
                        -decreased excretion of cephalosporins and resultant increased serum levels

Nursing Consideration
            -Check for allergies to PCN and/or to other cephalosporins
            -Lab work to assess liver and renal function
            -Check C&S prior to administration of any antibiotic
            -Infuse IV cephalosporins over at least 30 minutes to avoid pain or irritation
            -Observe for hypersensitivity reaction

Client Teaching
            -report S/S of Superinfection (mouth ulcers, discharge from anal or genital areas)
            -buttermilk and/or yogurt can help to prevent Superinfection
            -take complete course of ABX
            -take food if GI upset
            -report side effects from PO cephalosporins (anorexia, N/V, HA, dizziness, itching, rash)


Interesting Finding: The most frequent cause of community-acquired, uncomplicated Urinary Tract Infections (UTIs) is enterobacteria, mainly Escherichia coli (E.coli).  According to Garcia-Rodrigues & Bellido (2000), resistance of E. coli to the most commonly used antibiotics, such as, sulfonamides and trimethoprim/sulfamethoxasol, is near 50%. This problem led to the developments of oral cephalosporins. Currently, there are three generations of oral cephalosporins available to treat community acquired, uncomplicated UTIs. The cephalosporins’ pharmokinetics allows for “infrequent dosing intervals and good urinary levels” (Rodrigues & Bellido, 2000, p. 74), thus the bacteria gets destroyed.



References:

García-Rodríiguez, J. A., & Bellido, J. (2000). Oral cephalosporins in uncomplicated urinary tract infections. Clinical Microbiology & Infection, 673.  
Kee, J. L., Hayes, E. R., & McCuistion, L. E. (2012). Pharmacology. A nursing process approach. St. Louis, MO: Elsevier.
           


3 comments:

  1. Cephalsporins are always the hardest drug class because of the volume of drugs and the many differences in coverage between the classes. Think of cephalsporins as covering gram positive organisms and as you move from 1st to 4th generation the coverage expands to cover more gram negative bugs. Cefazolin (also known as Kefzol or Ancef) is used skin infections and pre op prophylaxis. Cefoxitin had a broader coverage including anaerobic organisms which come into play in intraabdominal infections. Claforan does cover some gram negatives but it does NOT cover pseudomonas very well. Ceftriaxone is a work horse abx used for UTIs and pnuemonia primarily. Good news about this drug is that it seems to have done very well with resistance over time. Cefepime, the 4th gen has extensive gram negative coverage including pseudomonas. The one thing to keep in mind about cephalosporins is the potential for cross reactivity in those with pencillin allergies. Often times this is overstated. The studies that showed higher incidence of rxn in those with PCN allergies were done using older 1st generation cephalsporins no longer used. The further you get from 1st generation (ie. 3rd,4th gen) the lower the chance of rxn. What I always keep in mind is what was the severity of the reaction with PCN. If it was a simple rash, I don't usually bat an eyelash. If it is swelling of any sort I contact a provider to have a conversation with a potential alternative option.

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  3. Mr. Dailey, thank you very much for your time and the valuable feeback you gave us.

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