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Antibiotics: Part I 1. Penicillins 2. Macrolides 3. Tetracylines 4. Glycyclines 5. Carbapenems Antimicrobial Objectives Part I and Part II 1. Discuss the general principles of antibiotic therapy. 2. Explain how antibiotics work to rid the body of infection. 3. Discuss the pros and cons of antibiotic usage. 4. 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 Introduction to Antibiotics: Penicillins, Macrolides, Tetracyclines & Carbapenems Match the Drug to the Bug!! Penicillins (some are SENSITIVE to penicillinase producing bacteria and some are RESISTANT) Macrolides Tetracyclines NARROW SPECTRUM Gram (+) only BROAD SPECTRUM, but many bacteria now resistant erythromycin *penicillin V (PenVeeK) (po) azithromycin (Zithromax) (po/IV) (EES) (po) *amoxicillin (Amoxil) (po) doxycycline (Vibramycin) (po) minocycline (Minocin) (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) “INEFFECTIVE” by bacteria that secrete penicillinase Glycyclines – newer and less resistant *procaine penicillin (IM/IV) ***penicillinase sensitive abx – Abx is rendered Carbapenems + penicillinase resistant abx – Abx is “EFFECTIVE” against bacteria that secrete pencillinase meropenem (Merrem) 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 1. VRE (enterococci) 2. MRSA (staph aureus) 3. 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? MOA: Inhibits cell wall synthesis (bacteriocidal) by interrupting the enzyme needed for bacterial cell division Narrow spectrum However, bacteria that can produce PENICILLINASE render the natural penicillins INEFFECTIVE Natural penicillins are effective against mild to moderate infections (strep & staph) 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 the is destroyed by BACTERIA bacteria that produce penicillinase OR 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 Milky color and less painful *penicillin V (PenVeeK) (PO) Penicillin Pearls: (P) longer duration 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 Common drugs: amoxicillin (Amoxil) (po)most commonly Rx penicilinase Therapeutic uses: treatment of sinusitis, otitis media, and bacterial endocarditis prophylaxis Otitis media = Ear infection Frontal sinusitis PENICILLINASE RESISTANT PENICILLINS Betalactam ABX that CAN destroy betalactamase sooo… EFFECTIVE against pencillinase/betalactamase producing bacteria Commonly rx drugs *dicloxacillin (Dynapen) (PO) These agents ARE effective against gram + betalactamase/penicillinase producing bacteria 1/3 of all otitis media bacteria now produce penicillinase Therapeutic Uses: to treat serious infections: bone and joint, CNS, endocarditis, septicemia Anti-staphlococcal penicillin= EFFECTIVE against infections caused by staph..MRSA Staph Aureus Infections Staph r/t illnessess Mild to severe skin infections Toxic shock syndrome Food poisoning 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 MRSA Skin Infections Penicillinase /betalactamase INHIBITORS Combination of a broad spectrum penicillin (amoxicillin) WITH a betalactamase inhibitor (clavulanic acid) Three betalactamase inhibitors 1. Broader spectrum 2. 3. Effective against gm (+), gm (-), anaerobes, AND betalactamase producing bacteria Clavulanic acid Sulbactam Tazobactam Extended Spectrum Penicillins Beta-Lactamase Inhibitors Oral: amoxicillin + clavulanic acid = Augumentin Parenteral: 1. ampicillin + sulbactam = Unasyn 2. piperacillin + tazobactam = 3. ticarcillin + clavulanic acid = Timentin Zosyn ** Most beta-lactam abx are excreted via the kidneys. Important to assess renal function. Penicillins: Newest Extended Spectrum Penicillin Common drug; *carbenicillin (Geopen) (IV, IM, po) 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 Penicllins: Summary Slide 1. NARROW spectrum (gram +) penicillinase SENSITIVE Procaine Penicillin PenVeeK 2. NARROW spectrum (gram +) penicillinase RESISTANT anti-staph penicillins dicloxacillin (Dynapen) 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) 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 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 Drug interactions: E-mycin can INHIBIT the metabolism of many other drugs. (theophyllin, warfarin, seizure drugs) Common drugs *erythromycin (many trade names E-mycin, eryped, EES) Newer macrolide azithromycin (Zithromax) Erythromycin is MR YUK! Tastes bad and causes diarrhea Zithromax has duration, can be given QD Tetracyclines protein synthesis – bacteriostatic True “broad spectrum” antibiotics, however many bacteria have developed RESISTANCE Distributed well in body – crosses the BBB so WILL reach CSF Effective against MOA: inhibit bacterial Some Gram (+) Some Gram (-) Rickettsia Mycoplasma Chlamydia H. pylori (stomach bacteria that causes peptic ulcer 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 Do not give to children under 8 years Many Adverse Effects! GI irritation Photosensitivity Superinfections Hepatoxicity Renal toxicity In children – discoloration of teeth, depression of bone growth Known teratogenic drug Blood dyscrasias Therapeutic uses: Drug of choice for chlamydia, rickettsia infections, Lyme disease, Rocky Mountain spotted fever Often used to treat acne and serious skin infections Tetracyclines Look for “cycline” suffix 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 meropenem (Merrem) ULTRA broad spectrum IV route only (phlebitis common) Used to treat serious mixed infections Carbapenems 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!!