Antibiotics

• Penicillino 1929 – Sir Alexander Flemingo Methicillin 1st semi-synthetic produced in late 1950’s b/c of Beta-

lactamase resistance by stapho Bind to Penicillin-Binding Protein on bacteriao Coverage:

Natural Penicillins (Pen G and Pen V)• Strept• Most enterococci• Non-penicillinase-producing staph (rare)• Non-penicillinase-producing gonococci• Anaerobes, other than Bacteroides

Amino Penicillins (Ampicillin and Amoxicillin)• Strept• Enterococci (better)• Gram – organisms E. Coli, Proteus, Shigella, Salmonella• Not very active against staph

Semi-Synthetic Penicillins (Methacillin, Nafcillin, Oxa/Cloxa/Dicloxa cillin)

• Staph (all but MRSA)• Strept

Expanded Spectrum Penicillins (Ticarcillin, Pipercillin, Carbenicillin)

• Increased Gram – spectrum: most enterobacteria and Pseudomonas

• Strept• Not very active against staph

Penicillin/B-Lactamase combo (Timentin, Augmentin, Zosyn, Unasyn)

• Staph (not MRSA)• Anaerobes, including bacteroides• Gram –

• Natural Penicillins

o PEN G (IV/IM) Not used very often for LE infections Used for Gas gangrene caused by clostridium (2 million units q2-

4h IV)o PEN V (PO)

250-500 mg PO qid

• Amino Penicillinso AMPICILLIN (PO, IM, IV)

Increased gram – coverage, but more adverse reactions (rash, diarrhea)

250-500 mg PO qid 2g IV q 4-6 h

o AMOXICILLIN (PO) Same indications as AMP, better PO absorption 250-500 mg PO tid

• Semi-Synthetico NAFCILLIN (IV)

Very effective against Staph (not MRSA) Parenteral Penicillin of choice for moderate to severe staph infxns. 1-2 g IV/IM q4-6h

o CLOX/DICLOXICILLIN (PO) Same coverage as NAF Better PO coverage 250-1000 mg PO qid, depending on severity of infection

• Expanded-Spectrumo TICARCILLIN (IV)

Great coverage of Pseudomonas Watch metabolites, as this drug has very high Na load… possible

development of hypokalemia, hypernatremia, and fluid retention Typically combined with aminoglycoside and/or clindamycin 3g IV q4-6h, check creatinine clearance (under 60 ml/min, increase

interval)o PIPERCILLIN

Good coverage of Pseudomonas Usually combined with aminoglycoside 3-4 g IV q4-6h

• Combo Drugso 3 beta lactamase inhibitors: clavulanic acid, sulbactam, tazobactamo TIMENTIN (Ticarcillin/Clavulanic Acid)

3.1 g IV q6-8h 3 g Ticarcillin + 100 mg Clavulanic Acid covers most staph (not MRSA), b-lactamase

E.Coli/Klebsiella/Haemophilis/Salmonella, excellent against anaerobes like Bacteroides fragilis

watch metabolites

1 potential DOC for empiric therapy of diabetic foot infections (though not used as much any more since creation of Zosyn)

o AUGMENTIN (Amoxicillin/Clavulanic Acid) 250 mg, 500 mg, 875 mg tablets all with 125 mg CA 500-875 mg PO bid Similar coverage to Timentin High incidence of diarrhea or PMC Out patient therapy for mild-moderate Diabetic foot infections DOC for outpatient tx of human or animal bites

o UNASYN (Ampicillin/Sulbactam) 2:1 ratio of Ampicillin:Sulbactam 1.5-3g IV/IM q6h Similar coverage to Augmentin Empiric therapy of moderate-severe DFI when Gram Stain reveals

predominately gram + organismso ZOSYN (Pipercillin/Tazobactam)

3.375 g IV q6h 4.5 g IV q8h, especially if pseudomonas suspected Current DOC for moderate-severe DFI, especially if broader

spectrum desired Severe bite wound infections

• Cephalosporinso 4-member beta lactam ring + 6-member dihydrothiazine ring… different

Abx have different side chainso 4 generations: 1st better against gram +, 2nd designed for better coverage

against H. influenzae, 3rd best against gram -, and 4th good against gram – with some gram + coverage

• 1st Generationo Covers:

Staph aureus (not MRSA) Strept Gram - : E.coli, P. mirablis, some Klebsiella Anaerobes: Pepto and Peptostreptococcus

o ANCEF (Cefazolin, Kefzol) 1-2g IM/IV q8h, check renal function DOC for initial empiric treatment of many community-acquired

infections of LE Prophylaxis of LE surgery

o KEFLEX (Cephalexin, Keftab) Similar coverage to ANCEF, but PO dose 250-500 mg PO bid-qid Outpatient therapy of many community-acquired infections

o DURICEF (Cefadroxil) Longer serum levels than keflex, so longer dosing schedules 500 mg PO q12h or 1 g PO q24h 1 g PO q12h for more serious infections

• 3rd Generationo Covers:

Staph (less effective) Strept (similar to 1st and 2nd gen) Gram – rods Gonococci Variable coverage of bacteroides and pseudomonas depending on

drugo ROCEPHIN (Ceftriaxone)

Longest ½ life of any cephalosporin (7-8 hrs) 1-2 g IM/IV q12-24h DOC for infections caused by Gonococci

• Used empirically in young adult presenting with clinical symptoms of septic arthritis

DOC for Lyme Diseaseo FORTAZ (Ceftazidime, Tazicef, Tazidime)

Most active Cephalosporin against Pseudomonas Less activity against Gram + organisms 1g IM/IV q8h for skin infections 2 g IM/IV q12h for bone and joint infections Can be used as a single agent therapy against Pseudomonas

o OMNICEF (Cefdinir) Great coverage of Gram + organisms (staph and strept) Good activity against common community acquired Gram -, but

not covering Enterobacteria or Pseudomonas 300 mg PO bid for skin infections 600 mg PO qd for respiratory tract infections

• 4th Generationo Covers:

Staph and Strept Gram – including Pseudomonas

o MAXIPIME (Cefepime) 1-2 g IV q12h

• Carbapenems

o Potent, broad-spectrum abx, that are resistant to most B-lactamaseso PRIMAXIN (Imipenem/Cilastatin)

Imipenem metabolized through kidney, so Cilastatin added, which is a renal dihydropeptidase inhibitor, to prevent early hydrolysis of imipenem

Extremely potent Abx with broadest spectrum of any antibiotic “Gorillamycin”, though expensive

Covers:• Most gram + aerobes and anaerobes• Most gram – organisms, except resistance found in B.

cepacia, S. maltophilia, and some strains of Pseudomonas• Acinetobacter baumanii• Good against most anaerobic bacteria, including all

bacteroides and clostridia, with exception of C. difficile Adverse reactions: seizures 500 mg IV q6-8h Empiric therapy of life- or limb-threatening infections in diabetic

patient, including necrotizing fasciitiso INVANZ (Ertapenem)

Equally effective against Gram + and Gram -, better against enterobacter, not effective against pseudomonas

1 g IM/IV q24h (once daily dosing) Equally effective as Zosyn for diabetic foot infections

• Monobactamso AZTREONAM (Azactam)

Only covers Gram – aerobes, including Pseudomonas 1-2 g IV q8h Can replace aminoglycosides for severe gram – infections Often mixed with Clinda in mixed infections

• Aminoglycosideso Mainstay in the treatment of severe gram – infectionso Significant toxicity: Ototoxicity (non-reversible), Nephrotoxicity

(reversible), and NM junction blockade (reversible)o Tricky dosing schedules: need to check creatinine clearance and adjust

dose appropriatelyo Coverage:

Excellent against aerobic gram – bacteria (pseudomonas) Gentamycin best against serratia Tobramycin best against pseudomonas Amikacin reserved for infection resistant to above 2 Also covers staph (given for Community-Acquired MRSA in peds) No activity against anaerobes

o Creatinine Clearance = (140-age) x weight in Kg/ Serum creatinine x 72 (x .85 for women)

o Multiple dose schedule: 2mg/kg loading dose of Gent or Tobra 5-7 mg/kg/day q8-12h maintenance dose Must check peaks and troughs as well and adjust dosage as needed

o Single Daily Dose: 5-7 mg/kg for Gent of Tobra

• Anti-Anaerobeso Anaerobes include:

Clostridium Bacteroides Peptococcus Peptostreptococcus Fusobacterium

o FLAGYL (Metronidazole) Bactericidal against almost all gram – anaerobes including B.

fragilis, less effective against gram + anaerobes Adverse Rxn: Disulfiram-like rxn with EtOH, seizures 500 mg PO tid-qid 15 mg/kg loading dose IV + 7.5 mg/kg IV q6-8h Limited use in LE infections, sometimes in combo DOC for Pseudomembranous Colitis caused by C. difficile

o CLINDAMYCIN (Cleocin) Covers:

• Most gram + organisms, including Staph (not MRSA) and Strept

• Most anaerobes, including bacteroides Most common cause of Pseudomembranous Colitis 600-900 mg q8h IV/IM 150-300 mg bid-tid PO NO DOSAGE CHANGE REQUIRED FOR RENAL FAILURE

(metabolized in liver) Uses:

• Outpatient oral therapy of Staph infections if patient allergic to penicillin and cephalosporin

• PO therapy of mildly infected diabetic ulcerations• Combo with quinolone for severe diabetic infections• Possible DOC for Staph Osteomyelitis good penetration

into bone and leukocytes, and ability to dissolve glycocalyx

• Anti Gram + o VANCOMYCIN (Vancocin)

Used much more recently due to increase in MRSA IV and PO (only for pseudomembranous colitis treatment if flagyl

fails) Covers:

• All Gram + organisms (including MRSA and MRSE)• Enterococci• Other streptococci• Gram + anaerobes, including clostridium• Cornyebacteria

Adverse Reactions: Ototoxicity, Nephrotoxicity, “Red Man Syndrome” (release of histamines from mast cells with vanco infused to quickly infuse vanco over 45-60 minutes)

1g q 12 hours IV for serious infections (max 2 g/day) 125 mg qid PO for pseudomembranous colitis Peak: 20-50 ug/ml, Trough <10 ug/ml DOC for MRSA and MRSE infections Gram + infections in patient allergic to penicillin and

cephalosporin Surgical prophylaxis for joint implants

o SYNERCID (Quinipristin/Dalfopristin) Covers:

• Enteroccocus faecium, including VRE• Staph, including MRSA

Adverse Rxn includes phlebitis at IV site, so give drug via central line or PICC line only

7.5 mg/kg q8-12h through central IV line Extremely expensive ($3000 for 10 days)

o ZYVOX (Linezolid) Extremely effective against all Gram + organisms, including

MRSA and VRE PO dosage and low adverse reactions makes this more common

used drug over synercid Adverse Reactions: Thrombocytopenia 600 mg bid IV or PO Still expensive, so only use if necessary

• Quinoloneso CIPROFLOXACIN (Cipro)

Covers:• Excellent coverage of all common Gram – organisms

• Originally thought to be a good coverage of Staph, has shown over time to develop multiple staph resistant strains

Adverse Rxn:• Some neurotoxicity or photosensitivity common• Will potentiate caffeine• Causes degeneration of cartilage, so contraindicated in

children• Associated with tendonopathies and ruptures, especially

Achilles 500 mg bid PO for mild-moderate infections 750 mg bid PO for severe infections and osteomyelitis Indicated for severe gram – infections and nosocomial infections;

PO therapy of osteo (especially pseudomonas osteo); diabetic foot infections if in combo with clindamycin or flagyl

o LEVAQUIN (Levofloxacin) Better activity against Staph and Strept than Cipro Less activity against Pseudomonas, but still covers other gram – Same adverse reactions and cipro 500 mg qd PO/IV for mild-moderate infections 750 mg qd PO/IV for severe skin infections Quinilone of choice for most LE infections due to once daily

dosing, better gram + coverage, and FDA approval for skin infections (diabetic foot infections)

o AVELOX (Moxifloxacin) Newer FDA approved drug for LE infections Better against Gram + 400 mg qd PO/IV

• Sulfonamideso BACTRIM, SEPTRA (Trimethoprim/Sulfamethoxazole)

Fixed Trimethoprim:Sulfa ratio of 1:5 Covers:

• Static against all organisms• Staph, including MRSA• Some strept• Enterococci• Excellent against gram -, except Pseudomonas and Serratia

Careful if patient allergic to “sulfa” drugs 1 tab of 160 mg: 800 mg bid PO PO therapy of staph infections or gram – infections in penicillin

allergic patients, possible MRSA coverage

• Macrolides

o ERYTHROMYCIN Covers:

• Staph (not MRSA) and Strept (not enterococci)• Some gram + and Gram – anaerobes (not bacteroides)

250-500 mg qid PO 1 g q6h IV in 100 ml of solution (slowly infused) Used for community-acquired infections of staph and strept in

patients allergic to Penicillinso ZITHROMAX (Azithromycin)

Covers: • Staph and Strept• Limited gram – activity, covers proteus and E.coli

Unique dosing:• 500 mg (2 pills) on day 1, then 250 mg once daily for 4

days (“Z-Pack”) Short-term convenient dosing good for non-compliant patients Used for penicillin-allergic patients with mild-moderate skin

infectionso BIAXIN (Clarithromycin)

Popular drug for respiratory infections Similar coverage with better Gram + coverage than Zithromax More drug interactions possible and more GI issues 250-500 mg bid PO

• Tetracyclineso TETRACYCLINE/DOXYCYCLINE/MINOCYCLINE

Broad spectrum, bacteriostatic Covers:

• Staph and Strept (no enterococci), Mino covers MRSA• Some gram – and anaerobe coverage• Treatment of unusual bugs:

o Borrelia burgdorferi (Lyme Disease)o Actinomyces (Madura Foot)o Mycobacterium marinum

Tetra: 250-500 mg qid PO Mino and Doxy: 100 mg q12h PO Minocycline PO DOC for MRSA infection when TMP/SMX is

resistant or linezolid is too expensive. Treatment of unusual bugs listed above

LISTS:

Gram Stain: Gram + is purple Gram – in pink Order: Crystal violet Iodine Alcohol Safarin

Gram + Cocci Gram – Rods Anaerobes Gas Forming Staph E. Coli Clostridium “BECKS +++”Strept Pseudomonas Bacteroides BacteroidesEnterococci Hemophilus Peptococcus E. ColiMicrococci Klebsiella Peptostreptococcus Clostridium

Serratia Fusobacterium KlebsiellaProteus Staph/StreptSalmonella SerratiaPasteurella Fusobacterium

PeptococcusPeptostreptococcus

Anti-Pseudomonal Drugs Anti-MRSA Anti-VRE “FAT-CIA” Vanco SynercidFortaz Synercid ZyvoxAztreonam ZyvoxTicarcillin BactrimCipro MinocyclineImipenem Gentamycin (peds)AminoglycosidesPipercillin (Zosyn)

Drugs not requiring renal dosing: Clinda, Erythro, Chloramphenicol, Cefoperazone