Lecture 7

Chapter 25
Antibacterials:
Penicillins & Cephalosporins

Antibacterials
Antibacterials/antimicrobial drugs - Substances that inhibit
the growth of or kill bacteria or other microorganisms
(microscopic organisms = bacteria, viruses, fungi,
protozoa)
Bacteriostatic = Inhibits growth of bacteria
Bactericidal = Kills bacteria
Peaks & Troughs = Serum antibacterial levels for drugs w/
a narrow therapeutic index
- Too high = drug toxicity (Peak - 1 hr. after drug infused)
- Too low = therapeutic range (Trough - before dose)

Antibacterials
Mechanism of Action:
1. Inhibition of cell wall synthesis - Bactericidal
2. Alteration in membrane permeability - Cidal or
Static
3. Inhibition protein synthesis - Cidal or Static
4. Inhibition of bacterial RNA & DNA - Inhibits
synthesis of RNA & DNA
5. Interferes with metabolism in the cell - Static

Antibacterials
Drugs 1. Penetrate bacterial cell wall in sufficient
concentrations
2. Affinity to the binding sites on the bacterial cell:
- Time drug remains at binding sites = effect
- Time controlled by pharmacokinetics

Antibacterials

Pharmacodynamics -

- Concentration at site or exposure time for drug plays an

important role in bacteria eradication
- Duration of time for use of antibacterial varies according
to type of pathogen, site of infection & condition of host
- With some severe infections - continuous infusion more
effective than intermittent
- Body defense & drugs work together to stop infectious
process
- Effect = drug & hosts defense mechanisms

Effects of concentrated drug dosing

Antibacterials
Bacterial Resistance - result naturally or may be acquired
* Natural (inherent) = w/o previous exposure to antibiotic
ie. pseudomonas resistant to Penicillin G
* Acquired = prior exposure to antibacterial
ie. staph aureus was sensitive to PCN G, now its not
Nosocomial infections - infections acquired while clients
are in the hosp. Many are mutant strains resistant to many
antibacterials
Prolonged hospital stay
Antibacterial resistance occurs when antibiotics are used
frequently

Antibacterials
Culture & Sensitivity - Bld test done to determine effect
drugs have on a specific organism
Culture = organisms responsible
Sensitivity = what antibiotic will work best
Narrow & Broad Spectrum
Narrow - primarily effective against 1 type of organism
Broad - effective against both gram + & gram - organisms
* Used before isolating organism through C & S
* Not as effective as narrow spectrum against those
single organisms

Antibacterials
Penicillins (PCN)
From mold genus Penicillium - miracle drug from
WWII
A beta-lactum structure (beta-lactum ring) interferes w/
bacterial cell wall synthesis by inhibiting the bacterial
enzyme necessary for cell division & synthesis
Bacteria die of cell lysis (breakdown)
Both static & cidal in nature
Mainly referred to as beta-lactum antibiotics (enzymes
produced by bacteria that can inactivate PCN Penicillinases = beta-lactamases which attack PCN

Antibacterials
Penicillins
Natural Penicillins
Penicillin G, Penicillin V, Procaine, Bicillin
- Good gram +, fair gram - , good anaerobic
- PCN G = more effective IV or IM, but painful d/t
aqueous solution
- PCN V = PO; peak 2 - 4 hrs

Antibacterials
Penicillins
Aminopenicillins (Broad Spectrum)
Amoxicillin (Amoxil), Ampicillin (Omnipen),
Bacampicillin HCL (Spectrobid)
- Gram + & Gram - Costlier
- Inactivated by beta-lactamases = ineffective
against Staphylococcus aureus (staph. A)
- Amoxicillin = most prescribed PCN derivative for
adults & children

Antibacterials
Penicillins
Penicillinase - Resistant Penicillins
Methicillin (Staphcillin), Nafcillin (Unipen),
Oxacillin (Bactocil)
- Used to treat penicillinase-producing Staph A.
- Gram + , not effective against Gram - IV & PO

Antibacterials
Penicillins
Extended - Spectrum Penicillins
Carbenicillin (PO), Mezlocillin, Piperacillin,
Ticarcillin, Ticarcillin-clavulanate (Timentin) - IM
& IV
- Broad spectrum - good gram (-), fair gram (+)
- Good against Pseudomonas aeruginosa
- Not penicillinase resistant

Antibacterials
Penicillins
SE & adverse reactions of Penicillins
1. Hypersensitivity - mild or severe
Mild = rash, pruritus, & hives - Rx w/ antihistamines
Severe = anaphylactic shock - occurs w/ in 20 min. - Rx
w/ epinephrine
2. Superinfection - secondary infection when normal
microbial flora of the body disturbed during antibiotic Rx
Mouth, resp. tract, GI, GU or skin - usually fungus

3. Organ toxicity - esp. liver & kidneys where drugs

metabolized & excreted (aminoglycosides)

Antibacterials
Cephalosporins
From a fungus Cephalosperium acremonium
- Gram (+) & gram (-)
- Resistant to beta - lactamase
- Bactericidal - action similar to PCNs
- 4 groups (generations) - each effective against a broader
spectrum of bacteria
- about 10% of people allergic to PCN also to allergic to
cephalosporins
- Action - inhibits bacterial cell wall synthesis
- IM & IV - onset = almost immediate

Antibacterials
Cephalosporins
1st Generation Cephalosporins - cefadroxil
(Duricef) & cephalexin (Keflex) - PO; Cefazolin
(Ancef) & cephalothin (Keflin) - IM

- Gram (+), & gram (-)

- Esp. used for skin/skin structure infections
- Keflin used for resp, GI, GU, bone, & joint
infections

Antibacterials
Cephalosporins
2nd Generation Cephalosporins - cefaclor (ceclor) PO, cefoxitin (Mefoxin), cefuroxime (Zinacef),
cefotetan (Cefotan) - IM & IV

- Gram (+), slightly boarder gram (-) effect than 1st

generation
- for harder to treat infections

Antibacterials
Cephalosporins
3rd Generation Cephalosporins - cefotaxime
(Claforan), ceftazidime (Fortaz), ceftriaxone
(Rocephin), cefixime (Suprax) - IM or IV
- More effective against gram (-), less effective against
gram (+)
- for harder yet to treat infections

4th Generation Cephalosporins - cefepime

(Maxipime) - IV or IM
- Resistant to most beta-lactamase bacteria
- greater gram (+) coverage than 3rd generation

Ch. 26 - Antibacterials
Macrolides, Lincosamides, Vancomycin
All differ in structure, but similar spectrums of antibiotic
effectiveness to PCN
Used as PCN substitutes, esp. w/ people allergic to PCN
Erythromycin frequently prescribed if hypersensitive to
PCN
Macrolides - Erythromycin, Azithromycin (Zithromaz),
Clarithromycin (Biaxin) - PO/IV, Dirithromycin (Dynabac) PO - Broad spectrum of activity

- Low to mod dose = bacteriostatic

- high doses = bactericidal
SE = GI disturbances, Allergic rxns = Hepatotoxicity

Antibacterials
Lincosamides
Clindamycin (Cleosin), Lincomycin (Lincorex)
- PO, IM, IV
- Inhibit bacterial protein synthesis
- Static & cidal actions depending on drug
dosage
- effective against most gram (+), no gram (-)
- Clindamycin more effective than lincomycin

Antibacterials
Vancomycin
Glycopeptide bactericidal antibiotic - IV
- Use: Drug resistant Staph A., cardiac surgery prophylaxis for clients w/ PCN allergies
- SE = Ototoxicity - damage to auditory branch of
8th cranial nerve permanent hearing loss or loss
of balance & Nephrotoxicity
- Serum Vanco levels drawn to minimize toxic
effects

Antibacterials
Tetracyclines
Tetracycline, Doxycycline (Vivbamycin), Minocycline
(Minocin)
- Broad spectrum - Gram (+) & gram (-) bacteria
- Bacteriostatic
- Wide safety margin, but many side effects
- Primarily used for skin/skin structure infections
- Also used to treat Helicobacter pylori (H. pylori) bacterium in stomach that can cause peptic ulcers
- Tetracycline mostly

Antibacterials
Tetracyclines
Considerations
- SE = Photosensitivity - sunburn rxn
- Should not be given to children < 8 yrs or to
women in last trimester of pregnancy Irreversibly discolors permanent teeth
- Tetracycline during 1st trimester of pregnancy can
cause birth defects
- Take on an empty stomach - antacids & dairy
products prevent absorption of the drug

Antibacterials
Aminoglycosides
Amikacin (Amikin), Gentamicin (Garamycin),
Tobramycin (Nebcin), Netilmicin (Netromycin)
- Inhibits bacterial protein synthesis, cidal
- Gram (-) & some gram (+)
- Used to treat serious infections
- Cannot be absorbed from GI tract, cannot cross into CSF
- To ensure a desired bld level - IV use
- Narrow therapeutic range - Peak & Trough levels drawn
- SE = Ototoxicity, Nephrotoxicity

Antibacterials
Fluoroquinolones (Quinolones)
Ciproflaxacin (Cipro), Levofloxacin (Levaquin),
Ofloxacin (Floxin), Norfloxacin (Noroxin) - IV or PO
- Interferes w/ synthesis of bacterial DNA
- Bactericidal
- Broad spectrum - gram (-) & gram (+)
- Rx - UTIs, lower resp. infections, bone & joint
infections, GI, skin
- Wide safety margin
- CI - Children < 14 yrs

Chapter 27
Sulfonamides
One of the oldest - broad spectrum - gram - & gram +
First group of drugs used against bacteria
Bacteriostatic - inhibits bacterial synthesis of folic acid,
essential for bacterial growth
Alt. for people allergic to PCN
Use - UTIs, ear infections, newborn eye prophylaxis
- Not effective against viruses or fungi
PO, soln & ointment for ophthalmic use & cream
- Silver sulfadiazine (Silvadene) - for burns

Antibacterials
Sulfonamides
Special consideration - Drink fluids to prevent
crystalluria (d/t poor water solubility) & hematuria
SE - allergic response - skin rash & itching
- Anaphylaxis not common
- Bld disorders w/ prolonged use & high doses
- GI disturbances
- Photosensitivity

Chapter 28
Antitubercular, Antifungal
Peptides, & Metronidazole
Inhibit or kill organisms that case diseases
Tuberculosis (TB) - Caused by the acid-fast Bacillus Mycobacterium
tuberculosis - frequently referred to as the tubercle bacillus
- One of the major health problems in the world & kills more
people than any other infectious disease
- About 11/2 billion people have TB & dont know it
- TB in US until 1980s & AIDS d/t compromised
immune system

Antiinfective Agents
Tuberculosis
Transmitted by droplets dispersed in the air through
coughing & sneezing inhaled into alveoli (air sacs) of
lungs spread to other organs via blood & lymphatic
system
- Strong system = phagocytes stop multiplication of
tubercle bacilli
- Compromised system = tubercle bacilli spread

Antiinfective Agents
Tuberculosis
Drugs: Isoniazid (INH) - 1952, Rifampin
- Prophylactic therapy for persons close to TB, HIV +, a
+ TB skin test, young children in contact w/ active TB,
- Family members on Isoniazid 6 months to 1 yr
- Spectrum = Myobacterium tuberculosis, cidal
- Combo of Isoniazid & Rifampin = No bacterial resistance
& less Rx time = more effective
- SE = flu-like symptoms, neurotoxicity, hepatotoxicity,
Monitor drug therapy carefully

Antiinfective Agents
Antifungals (Antimycotics)
Topical - skin/mucus membranes (athletes foot)
Systemic - lung, CNS (pulmonary conditions, meningitis)
Fungi - Candida (yeast) - normal flora of mouth, skin,
intestine, vagina
Candidiasis = opportunistic infection - bodys defense
mechanism impaired allowing overgrowth of fungus
Drugs - antibiotics, contraceptives & immunosuppressives
may alter bodys defense mechanisms
- mild = vaginal yeast infection, severe = systemic infect.

Antiinfective Agents
Polyenes
Amphotericin B (Fungizone), Mystatin (Mycostatin)
Broad spectrum antifungal activity
Fungizone = IV administration
SE = Flushing, chills, N & V, dec. BP
Considered highly toxic - nephrotoxicity & electrolyte
imbalance poss
Nystatin = orally or topically for candidal infections
Swish & swallow to allow contact w/ mucus membranes

Antiinfective
Antifungal
Metronidazole (Flagyl) - treatment of various
disorders associated w/ organisms of GI tract - PO
and IV
SE = GI discomfort, Headache, depression (not
common)
Also used to treat H. pylori associated w/ peptic
ulcers

Math Problems
A dose of 200 mcg is ordered. The strength available is 0.3 mg. in 1.5 mL.
Convert mg to mcg.

1 mg = 1000 mcg

0.3 mg = 300mcg
200 mcg

1.5 ml. = X ml

300 mcg
2

1.5

= X

3
To give 200 mcg you must administer 1 ml.

1 ml
3

A dosage of 0.7 g. has been ordered. Available is a strength of

1000 mg. in 1.5 mL.
Convert g. to mg.
0.7 g = 700 mg
700 mg. X
1000 mg.
7
10

1.5 mL = X mL

1.5 mL

10.5
10

10.5 divided by 10 = 1.05

Round up to 1.1.

So administer 1.1 mL.