Antibiotics: Part I Penicillins Macrolides Tetracylines Glycyclines Carbapenems

Antimicrobial Objectives Part I and Part II Discuss the general principles of antibiotic therapy. Explain how antibiotics work to rid the body of infection. Discuss the pros and cons of antibiotic usage. Describe the signs and symptoms, diagnostic criteria, and common treatment of the superinfections: candidiasis and clostrium difficile colitis. 5. Discuss the MOA, indications, cautions, common and serious adverse reactions associated with selected antibiotic groups: Antibiotics Part I: Penicillins Macrolides Tetracyclines/Glycyclines Carbapenems Antibiotics Part II: Cephalosporins Sulfonamides Aminioglycosides Fluroquinolones Oxazolidinones Lincosamides

Match the Drug to the Bug!! Introduction to Antibiotics: Penicillins, Macrolides, Tetracyclines & Carbapenems Match the Drug to the Bug!!

Glycyclines – newer and less resistant Carbapenems Penicillins (some are SENSITIVE to penicillinase producing bacteria and some are RESISTANT) Macrolides NARROW SPECTRUM Gram (+) only Tetracyclines BROAD SPECTRUM, but many bacteria now resistant Glycyclines – newer and less resistant Carbapenems *procaine penicillin (IM/IV) erythromycin (EES) (po) doxycycline (Vibramycin) (po) meropenem (Merrem) *penicillin V (PenVeeK) (po) azithromycin (Zithromax) (po/IV) minocycline (Minocin) (po) *amoxicillin (Amoxil) (po) tigecycline (Tygacil) A derivative of minocycline = Glycycline +amoxicillin + clavulanic acid (Augmentin) (po) +dicloxacillin (Dynapen) (po) +piperacillin + tazobactam (Zosyn) (IV) carbenicillin (Geopen) anti-pseudomonas (IV) ***penicillinase sensitive abx – Abx is rendered “INEFFECTIVE” by bacteria that secrete penicillinase + penicillinase resistant abx – Abx is “EFFECTIVE” against bacteria that secrete pencillinase

PENICILLINS Natural and synthetic Penicillins are the most widely effective and extensively used antibiotics Structural component is a BETA-LACTAM RING The job of penicillin is to DESTROY the bacterial cell wall It does this by attacking the cell wall with its beta lactam ring….. Aka the penicillin missile contains a beta- lactam ring

Penicillin “missile” is its beta-lactam ring Bacteria after penicillin “attack”

What are penicillinase/betalactamase enzymes? Some bacteria ‘got smart’ and developed a defense an ENZYME that DESTROYS the penicillin beta lactam ring This “ANTI-MISSILE” aka the “ENZYME”– renders these bacteria RESISTANT to the penicillin Betalactamase enzymes that act directly on penicillin are known as “PENICILLINASES” Betalactamase enzymes that act on other antibiotic classes (cephalosporins) are known as “BETALACTAMASES” The “anti-missile” of resistant bacteria: penicillinase for penicillin betalactamase for cephalosporins

Bacteria resisting an antibiotic Superbugs in acute care VRE (enterococci) MRSA (staph aureus) Acinentobacter

Penicillins: Side Effects All Classes Allergic reactions including: urticaria, pruritus, and angioedema Most are mild, but about 10% of allergic reactions are lifel-threatening Treatment of acute allergic reaction includes: epinephrine, steroids, and antihistamines Some cross-sensitivity between cephalosporins and penicillins exist - so may see allergy to both Generally well tolerated with *GI effects (N-V-D) most common problem Nursing alert: always check allergy before administering penicillin. When giving IM, observe patient closely for at least 30 minutes Foods may decrease absorption angioedema

Urticaric Rash Typical urticaric rash from penicillin allergy Erythematous, maculopapular rash

What is the MOA of Natural Penicillins? Inhibits cell wall synthesis (bacteriocidal) by interrupting the enzyme needed for bacterial cell division Narrow spectrum Natural penicillins are effective against mild to moderate infections (strep & staph) However, bacteria that can produce PENICILLINASE render the natural penicillins INEFFECTIVE  These bacteria are known as “penicillin resistant bacteria” Natural penicillin was originally used to treat STAPH INFECTIONS but by 1953, 80% of all hospital strains of staph aureus were penicillin-resistant = (MRSA) Bacteria produce penicillinase making them resistant to natural penicillins

Natural Penicillins NARROW spectrum agents penicillinase SENSITIVE penicillins the PENICILLIN is destroyed by bacteria that produce penicillinase OR the BACTERIA are penicillin resistant Natural Penicillins *aqueous penicillin G (Bicillin) (P) Destroyed by gastric acid so cannot be given po short duration of action and very painful procaine penicillin (P) longer duration Milky color and less painful *penicillin V (PenVeeK) (PO) Penicillin Pearls: Effective against mostly Gram (+) bacteria, some gram(-) Derived from a mold or fungus Look for “cillin” suffix Injectable form given deep IM Prescribed in “units”

AMINOPENICILLINS BROADER spectrum action but NOT penicillinase resistant Have an amino group attached to their penicillin nucleus that makes them more effective against gram (-) bacteria Also still effective against some gram (+) bacteria Sensitive to penicillinase producing bacteria, so…. NOT effective against staph aureus (MRSA) which DO produce penicilinase Therapeutic uses: treatment of sinusitis, otitis media, and bacterial endocarditis prophylaxis Common drugs: amoxicillin (Amoxil) (po)- most commonly Rx Otitis media = Ear infection Frontal sinusitis

*dicloxacillin (Dynapen) (PO) PENICILLINASE RESISTANT PENICILLINS Betalactam ABX that CAN destroy betalactamase sooo… EFFECTIVE against pencillinase/betalactamase producing bacteria These agents ARE effective against gram + betalactamase/penicillinase producing bacteria 1/3 of all otitis media bacteria now produce penicillinase Anti-staphlococcal penicillin= EFFECTIVE against infections caused by staph..MRSA Commonly rx drugs *dicloxacillin (Dynapen) (PO) Therapeutic Uses: to treat serious infections: bone and joint, CNS, endocarditis, septicemia

Staph Aureus Infections Methicillin resistant staph aureus (MRSA) Bacteria that can cause SERIOUS infections. These bacteria are RESISTANT to methicillin/penicillins Rendering the penicillins ineffective Causes wound infections, urinary tract infections, pneumonia, sepsis Staph r/t illnessess Mild to severe skin infections Toxic shock syndrome Food poisoning

MRSA Skin Infections

Penicillinase /betalactamase INHIBITORS Combination of a broad spectrum penicillin (amoxicillin) WITH a beta-lactamase inhibitor (clavulanic acid) Broader spectrum Effective against gm (+), gm (-), anaerobes, AND betalactamase producing bacteria Three betalactamase inhibitors Clavulanic acid Sulbactam Tazobactam

Extended Spectrum Penicillins Beta-Lactamase Inhibitors Oral: amoxicillin + clavulanic acid = Augumentin Parenteral: ampicillin + sulbactam = Unasyn piperacillin + tazobactam = Zosyn ticarcillin + clavulanic acid = Timentin ** Most beta-lactam abx are excreted via the kidneys. Important to assess renal function.

Penicillins: Newest Extended Spectrum Penicillin Are important in treating SERIOUS GRAM (–) infections d/t Pseudomonas However, NO coverage against bacteria that produce betalactamase So not a good choice for staph MRSA infections Often used in combination with aminoglycosides Made by making a few changes in basic penicillin structure Common drug; *carbenicillin (Geopen) (IV, IM, po)

Penicllins: Summary Slide 3. BROAD spectrum (gram + and gram –) penicillinase sensitive aminopenicillins amoxicillin (Amoxil) 4. EXTENDED spectrum gram (+) and gram (-) AND penicillinase resistant amoxicillin + clauvalnic (Augmentin) pipercillin + tazobactam (Zosyn) 5.Newest Extended Spectrum Antibiotic anti-pseudomonas penicillin Pseudomonas serious Gm (-) carbenicillin (Geopen) 1. NARROW spectrum (gram +) penicillinase SENSITIVE Procaine Penicillin PenVeeK 2. NARROW spectrum (gram +) penicillinase RESISTANT  anti-staph penicillins dicloxacillin (Dynapen)

What is Pseudomonas? Pseudomonas is a gram (-) bacterium Newest extended spectrum: effective against gram (-); but NOT resistant to penicillinase producing bacteria Causes serious infections in hospitalized patients: Skin/surgical site Blood Pneumonia

Macrolides MOA: inhibit bacterial protein synthesis Bacteriostatic at low concentrations Bactriocidal at high concentrations PO or IV use only. Too painful to give IM! 1st Macrolide was erythromycin, which is known for its bad taste and GI upset

Macrolides (cont) Therapeutic uses: Narrow spectrum Mostly active against gram (+) organisms Suitable replacement for penicillin in hypersensitive pts * Used for “atypical” infections (chlamydia, mycoplasma, bacteria that commonly cause STDs and pneumonia Used to treat H pylori , bacteria that causes peptic ulcers

Macrolides *GI distress the most common complaint. GI motility Adverse Effects *GI distress the most common complaint. GI motility Superinfections Hepatotoxicity  effect of theophyllin, coumadin, and carbamazepine (anticonvulsant) Oral agents have a bad taste and many trade names have been developed trying to make more acceptable

Macrolides *erythromycin (many trade names Newer macrolide Common drugs *erythromycin (many trade names E-mycin, eryped, EES) Newer macrolide azithromycin (Zithromax) Zithromax has  duration, can be given QD Drug interactions: E-mycin can INHIBIT the metabolism of many other drugs. (theophyllin, warfarin, seizure drugs) Erythromycin is MR YUK! Tastes bad and causes diarrhea

Tetracyclines MOA: inhibit bacterial protein synthesis –bacteriostatic True “broad spectrum” antibiotics, however many bacteria have developed RESISTANCE Effective against Some Gram (+) Some Gram (-) Rickettsia Mycoplasma Chlamydia H. pylori (stomach bacteria that causes peptic ulcer MOA: inhibit bacterial protein synthesis –bacteriostatic Distributed well in body – crosses the BBB so WILL reach CSF

TETRACYCLINES Chemically related group of 5 antibiotics No milk with tetracyclines TETRACYCLINES Chemically related group of 5 antibiotics Bind (chelate) to Calcium and Magnesium and metallic ions to form insoluble complexes So co-administration with milk, antacids, or iron salts causes  absorption of antibiotic Not usually given to children younger than 8 years of age d/t adverse effects!

Tetracyclines Therapeutic uses: Do not give to children under 8 years Therapeutic uses: Drug of choice for chlamydia, rickettsia infections, Lyme disease, Rocky Mountain spotted fever Often used to treat acne and serious skin infections Many Adverse Effects! GI irritation Photosensitivity Superinfections Hepatoxicity Renal toxicity In children – discoloration of teeth, depression of bone growth Known teratogenic drug Blood dyscrasias

Tetracyclines Look for “cycline” suffix Interactions: Common drugs: doxycycline – (Vibramycin) (P), (PO) minocycline (Minocin) (PO) Interactions: absorption when given with milk, antacids, iron, or calcium

New Class: Glycylcline (2006) MOA a broad spectrum abx similar in structure to tetracycline Is a derivative of minocycline Blocks protein synthesis in bacterial cells  bacteriostatic

Glycycline tigecycline/Tygacil ADVANTAGE: does not have resistant seen in older tetracyclines BROAD SPECTRUM IV use only for complicated skin and intra-abdominal infections SE: similar to tetracyclines: photosensivity, GI upset, discoloration of teeth

Tygacil: for complicated skin and intra-abdominal infections IV only! Infected deep leg ulcer Staph cellulitis

Carbapenem IV route only (phlebitis common) meropenem (Merrem) ULTRA broad spectrum IV route only (phlebitis common) Used to treat serious mixed infections

Carbapenems Broadest spectrum of all Have a beta lactam structure Must be given IV Broadest spectrum of all Used for complicated abdominal infections, meningitis Well tolerated; with few adverse reactions Can be used to treat “MIXED INFECTIONS” Staph Gm (-) Gm (+)

That’s all Folks!!