Pharm CH 29

Bacteria:
single celled organisms

•Bacteria
reproduce by cell division about q 20 mins


•Most
have a rigid cell wall and the structure of the wall determines the shape of
the bacteria.

–Bacillus-rod
shaped

–Cocci- spherical

–Cocci in clusters-
staphylococci

–Cocci in chains-
streptococci

Another classification of bacteria involves staining.

•Gram staining is determined by the ability of the cell wall to retain a purple stain
by a basic dye.

Gram + bacteria turn purple (retain the dye)

Staphylococcus
aureus

Streptococcus
pneumoniae

Group B streptcoccus


Gram– bacteria not stained by dye

Neisseria meningitides

Escherichia coli

Haemophilus influenzae

Types of Antibiotic Therapy

•Empiric therapy: prior to definitive dianosis
prescribed antibiotic w/o test of cultures


•Prophylactic therapy:
treatment before a problem, ex. Amoxicilin when go to a dentist before oral treatment

•Therapeutic therapy:
Know exactly what it is and treat it with exact antibiotic

Beta-lactamase

•Many bacteria produce the enzyme beta-lactamase, which destroys beta-lactam antibiotics such as PCN ( penicilin) and cephalosporins.

Antibacterial Drugs

•Antibacterial, antimicrobial, antibiotics, are used interchangeably.

•Do not act alone:

–Natural body defenses ( immune system, if immune compromized very difficult to fight bacteria)

–Surgical procedures to excise infected tissue (remove dead tissue, form of debride)

–Dressing changes (when you change it, all the puss gets cleaned out, remains on the dressing)

•Obtained by either natural resources or manufactured.

•PCN marketed in 1945 ( mas marketed to soldiers , dying on the field)

•Sulfonamide a synthetic antibacterial introduced in 1935

Bacteriostatic/Bactericidal

•Bacteriostatic drugs inhibit the
growth of bacteria

•Bactericidal drugs kill bacteria

–Tetracycline and sulfonamides are bacteriostatic


–PCN and cephalosporins are bactericidal

–Some drugs can be both

Mechanisms of Antibacterial Action

•5 mechanisms of antibacterial action are responsible for the inhibition of growth
and destruction of microorganisms:

Pharmacokinetics (ADME)

•Antibacterial drugs must penetrate the cell wall with sufficient concentration and have an affinity to the binding sites on the bacterial cell.

–The longer it is there the better it works.

•Antibacterials that have a longer
half life usually maintain a greater concentration at the binding site;
therefore frequent dosing is not required.

–Remember steady state of antibacterials occur after the 4th or 5th half lives

Pharmacodynamics

•The drug concentration at the site and length of time at site plays an important
role in bacterial eradication.  Antibacterials drugs are used to
achieve the MEC necessary to halt the growth of a microorganism.

•With some severe infections, a continuous infusion regimen is more effective than
intermittent dosing because of the constant drug concentration and time
exposure.

Pharmacodynamics (con’t)

The effect of antibacterial drugs has on an infection depends not only on the drug
but also on:

•Age

•Nutrition

•Immunoglobulins


•WBC

•Organ function

•Circulation- if circulation is impeded- the drug may not be distributed properly to the infected area

if poor circulation the drug is not going there

Resistance to Antibacterials

•Bacteria may be sensitive or resistant to certain antibacterials.

–When bacteria are sensitive to a drug, the pathogen is inhibited or destroyed.

–If bacteria are resistant to an antibacterial, the pathogen continues to grow,
despite administration of the antibacterial drug.

•Resistance may result naturally (occurs without previous exposure)  or it may be acquired (prior exposure to the
antibacterial).

Resistance to Antibacterials

•Penicillinase, an enzyme produced
by the microorganism, is responsible for causing its Penicillin resistance (penicilinaze breaks down penicilin structure).

•Penicillinase metabolizes penicillin G,
causing the drug to be ineffective.

•Penicillinase-resistant penicillins that are effective against S. aureus are currently
available.

Nosocomial Infections

•Infections acquired while clients are hospitalized.

–In large healthcare institutions, there is a tendency toward drug resistance in
bacteria.

–Mutant strains of bacteria have developed, thus increasing their resistance to
antibiotics that were once effective against them.

Antibiotic resistance (con’t)

•Bacteria
can transfer their genetic instruction to another bacterial species.

•The other bacterial species becomes resistant to that antibiotic as well.

–Methicillin was the first penicillinase-resistant PCN developed.  

–MRSA –highly resistant bacteria became resistant not only to methicillin, but to all PCN’s
and cephalosporins.

–In 1981 seen in the community

–Methicillin no longer on the
market- drug of choice in tx
of MRSA vancomycin.

•VREF:
vanco resistant enterococci faecium


•MRSA
–reported strain resistant to vanvo-VRSA- If this becomes prevalent, a major medical
problem could result

•Linezolid (Zyvox), is effective
against MRSA, VREF, and PCN resistant strptococci.

•Synercid IV- used against
life threatening infections caused by VREF, tx of bacteremia.

•In development bacterial vaccines- the bacterial vaccine against pneumococcus has been effective in decreasing the occurrence of pneumonia and meningitis.

Remember

•When antibiotics are taken unnecessarily, incorrectly, or stops prematurely, one may
develop resistance to antibacterials.

•Antibiotics are ineffective against viruses

Cross- Resistance

•Can occur between antibacterial drugs that have similar actions such as the penicillins and cephalosporins.

•To assure the effectiveness of a drug prescribed for a certain microorganism,
culture and sensitivity testing is performed.

•A C&S can detect the ineffective microorganism present in a sample and what
drug can kill it.

C&S


•The organism causing the infection is determined by culture.

•The antibiotic the organism  is sensitive
to are determined by sensitivity.

Antibiotic Combinations

•Combination antibiotics should not be routinely prescribed or administered except for
specific uncontrollable infections.

–Usually a single antibiotic will successfully treat a bacterial infection

–Take C&S before beginning any antibiotic!!

Spectrums of Antibiotics

•Narrow Spectrum are primarily effective against one type of organism.

–Example: PCN, erythro are used to tx infections caused by
Gram + bacteria

–Broad Spectrum can be effective against Gram +/- organisms.

–Broad Spectrum ABX’s are frequently used to treat infections when the offending microorganisms has not been identified by C&S.

Penicillin

•A natural antibacterial agent obtained from mold genus Penicillium.

•PCN’s
beta-lactam structure interferes
with bacterial wall synthesis by inhibiting the bacterial enzyme that is necessary for cell division and cellular synthesis

Let’s Clarify


•Penicillians are mainly referred
to as beta-lactam antibiotics.

–Bacteria can produce a variety of enzymes, such as beta-lactamases, that can inactivate penicillin and other beta lactam antibiotics such as cephalosporins.

The beta lactamases, which attack penicillins, are called penicillinases

Penicillin G

•First PCN given PO and IM.

–PO only about 1/3 of the dose is absorbed

–Therefore given IM and IV- more effective in achieving a therapeutic serum penicillin
level.

–Short duration of action

–IM painful because it is an aqueous soln.

Penicillin V

•Next type produced

2/3 absorbed by GI tract however less potent than PCN G.

PCN V is effective
against mild to moderate infections, including anthrax.

•Overused/abused-staph
resistant- therefore the development of broad spectrum ABX with structures
similar to PCN were created. They too combat infections resistant to PCN G and V.

Broad Spectrum Penicillin
(not broad anymore, old name, now just Penicilin)

•Used to treat both Gram +/- bacteria.

•Not all that broad after all.

•Are effective against some Gram – organisms but these drugs are not penicillinase resistant.

•They are readily inactivated by beta-lactamases, thus ineffective against S. aureus


–Examples:

Amoxicillin (prototype for penicilin)

Ampicillin

Penicillinase-Resistant Penicillins

•Penicillinase-resistant penicillins  are used to treat penicillinase-producing S. aureus.

•Not effective against Gram – organisms and is less effective than penicillin G
against Gram + organisms.

Examples:
 
•Dicloxacillin sodium (Dynapen)

•Nafcillin

•Oxacillin sodium

Amoxicillin and Dicloxacillin

Amoxicillin: upper resp tract infections, Urinary Tract Infection (UTI), otitis media, sinusitis

Dicloxacillin: Staphylococcus aureus infection

Amoxicillin and Dicloxacillin

Mode of action: inhibition of cell wall
synthesis, bactericidal effect

Drug Interactions


•The broad spectrum penicillins (amoxicillin and ampicillin) may decrease the effectiveness of oral contraceptives (need to have barrier contraceptive risk for HIV)

•When PCN is mixed with an aminoglycoside in IV soln, the actions of both are inactivated.

Beta Lactamase Inhibitors

When a broad spectrum
Abx is combined with a
beta lactamase inhibitor, the
resulting antibiotic inhibits the bacterial beta-lactamases, making the antibiotic effective and extending its
antimicrobial effect.

•Three beta-lactamase inhibitors(not antibiotics):

–clavulanic acid
–sulbactam
–tazobactam


These are not given alone

Examples:

–amioxicillin/clavulanic acid (Augmentin)

–Ampicillin/sulbactam (Unasyn)

–Piperacillin/tazobactam (Zosyn)

Extended Spectrum Penicillins

•AKA antipseudomonal penicillins

•Broad spectrum penicillins

•Effective against Pseudomonas
aeruginosa (Gram- bacillus)
which is difficult to eradicate

•Also useful against
many Gram -  organisms example Klebsiella pneumoniae.

•These penicillins are not penicillinase resistant

–Examples:

•Piperacillin/tazobactam (Zosyn)

•Ticarcillin/clavulanate (Timentin)

Cephalosporins(sister and brother to penicilin 10% crosover sensitivity, same backbone as in penicilin)

•Like PCN, the cephalosporins have a beta-lactam structure and act by inhibiting the bacterial enzyme necessary
for cell wall synthesis. Lysis to the cell occurs, and the bacterial
cell dies.

•10% cross over sensitivity!

Generations

•Four groups of cephalosporins have been developed, identified as generations.

•Each generation is effective against a broader spectrum of bacteria.

NOT ALL CEPHALOSPORINS  are affected by the beta lactamases

First Generation Cephalosporins

•Destroyed by the beta lactamases

•Effective against gram + bacteria

•Effective against most gram – bacteria

–Cefadroxil (Duricef)

–Cefazolin sodium (Ancef)

–Cephalexin (Keflex)

Second Generation Cephalosporins

•Same effectiveness as first generation

•Not all are affected by beta lactamases(not destroyed by beta lactamaze)

•These antibiotics possess a broader spectrum against other gram – bacteria.

–Cefaclor (Ceclor)

–Cefotetan (Cefotan)

–Cefprozil monohydrate (Cefzil)

–Cefuroxime (Ceftin)

Cefazolin and Cefaclor

Therapeutic uses: resp, urinary, skin infections

Cefazolin: bone and joint
infections, genital infections, endocarditis

Cefaclor: ear infections,
certain gram – and gram + strains.

Cefazolin and Cefaclor

Mode of action:
inhibition of cell wall synthesis, causing cell death, bactericidal effect

Third Generation Cephalosporins

•Resistant to beta lactamases

•Most are effective in treating sepsis and many strains of gram – bacilli.

•Same effectiveness as first and second generations.

•Also effective against gram – bacteria and less effective against gram + bacteria

–Cefdinir (Omnicef)

–Cefixime (Suprax)

–Ceftazidime (Fortaz)

–Cefpodoxime (Vantin)

–Cefoperazone (Cefobid)

Ceftriaxone (Rocephin

Fourth Generation Cephalosporins

•Similar to third generation

•Most are effective in treating sepsis and many strains of gram – bacilli.

•Resistant to most beta-lactamase bacteria

•Broader gram + coverage than the third generations.

–Cefepime (Maxipime)

 Side Effects and Adverse Reactions

•GI disturbances (N/V/D)

•Alteration in blood clotting time (increased bleeding)

•Nephrotoxicity in individuals withpreexisting renal disorder.

Drug Interactions


•ETOH- alcohol

–Flushing(very miserable),
dizziness, headaches, N/V and muscular cramps