Flashcards in antibiotics Deck (76):
Five ways to categorize antimicrobial agents
• By the type of sensitive organism
• By a scope of sensitive organisms
• By a drug’s mechanism of action
• By a drug’s ability to kill a microorganism
vs. being able to only diminish
reproduction of the microorganism
• By the chemical structure of the drug
Categorizing antimicrobials by type of sensitive organism
◉ Bacteria (Antibiotic)
◉ Fungi (Antimycotic)
◉ Viruses (Antiviral)
◉ Other organisms
a. Mycobacterium b. Spirochetes
Categorizing antimicrobials by their mechanism of action
1. Inhibition of cell wall synthesis
2. Increasing permeability of cell membrane
3. Anti-metabolite action of a drug
4. Inhibition of microbial DNA or RNA synthesis
5. Inhibition of the action of microbial ribosomal subunits
Categorizing antimicrobial agents by ability to kill microorganisms
• -cidal is a suffix denoting ability to kill an microorganism (ex. bactericidal).
• -static is a suffix denoting ability of an agent to inhibit the proliferation of an organism (ex. bacteriostatic).
Naturally derived antibiotics
•Naturally derived antibiotics include the following drug classes:
Synthetic antimicrobial drugs
Sulfonamides and Quinolones
Microbial sensitivity tests
• Minimum inhibitory concentration (MIC)
• Minimum bactericidal concentration (MBC)
Minimum Bactericidal Concentration
lowest concentration of antibiotic required to kill the germ.
Minimum inhibitory concentration
Antimicrobials are usually regarded as bactericidal when the MBC is at least four times the MIC.
microbial resistance: Target inactivation
• Conjugation - Passage of genes from cell to cell allows for development of drug resistance to occur.
• Mutation - DNA of the microbe line is spontaneously modified.
• Transduction - Bacteriophage carries modified DNA into the microbe to confer resistance.
Pharmacokinetic factors that may dictate the drug of choice
Route of administration
Distribution of an antimicrobial into the target tissue is especially important.
Many drugs will not reach their MIC in certain tissues.
Host influences that may
dictate drug of choice
Patients with compromised immune systems may require -cidal agents.
Pus will inactivate some antimicrobials (i.e. the aminoglycosides).
• Hemoglobin in hematomas will inactivate some antimicrobials (i.e. the tetracyclines and penicillins).
• Abscesses are often acidic and some antimicrobials are inactive at a low pH (i.e. the macrolides).
•Development of additional infection or supra-infection
Categorizing antimicrobials by chemical structure
• Silver Sulfadiazine/ Silvadene (topical)
• Sulfacetamide (ophthalmic drops)
• ***Sulfamethoxazole/ Gantanol--folic acid
• Sulfamethoxazole with Trimethoprim/ Bactrim or Cotrim
Class: Sulfonamide antibiotic
MOA: Competitive antagonist of para-
aminobenzoic acid (PABA) which is used
by bacteria in the synthesis of folic acid.
Char: Sensitive organisms are those that
must synthesize their own folic acid. Broad spectrum antibiotic. Bacteriostatic. Distributed throughout all tissues of the body including the CSF.
Sulfamethoxazole/ Gantanol indications and SE
● Indications: Urinary tract infections, otitis media, bronchitis. Has largely been replaced by Trimethoprim Sulfa which has a broader spectrum of activity.
● Side effects: GI – upset stomach, N/V. Headache, skin rashes, and marked photosensitization.
Sulfamethoxazole with Trimethoprim/ Bactrim
● Class: Sulfonamide antibiotic in combination with an additional folic acid inhibitor.
● MOA: Interference with folic acid formation at a successive step to sulfonamides.
● Char: Sulfamethoxazole + Trimethoprim (in a 5:1 ratio) synergistically inhibits two steps in folic acid synthesis
Indications: Urinary tract infections, otitis media, sinusitis, bronchitis, pneumonia, . Also for MRSA
● Side effects: headache, nausea, diarrhea, Hypersensitivity is approximately 3x more common than with Sulfamethoxazole alone.
scary Sulfamethoxazole with Trimethoprim/ Bactrim SE
Side effects: Megaloblastosis, leukopenia, and thrombocytopenia - characteristics of folate deficiency – TMP-Sulfa most severe SE is Stevens Johnson syndrome (toxic epidermal necrolysis).
The Penicillins are a group of beta-lactam antibiotics used for susceptible Gram-positive organisms.
• β-lactam antibiotics work by binding to penicillin binding proteins (PBPs)on the bacteria and inhibiting the formation of peptidoglycan cross-linkage in the bacterial cell wall,
Allergic reactions to penicillin derivatives
There is an approximate 5% cross-sensitivity between penicillin derivatives and the Cephalosporins.
extreme caution with all β-lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.
Penicillins and penicillin congeners
• Penicillin G
• Penicillin VK
• Amoxicillin/ Amoxil***
• Ampicillin/ Ampicil, Omnipen
• Amoxicillin & clavulanate/ Augmentin ***
• Cloxacillin/ Cloxapen
• Dicloxacillin/ Diclox
• Methicillin/ Methicillin
• Class: Beta-lactam class antibiotic
• MOA: Beta lactam component binds to PBPs on
bacteria and thereafter inhibits cross linking of
components of bacterial cell wall.
• Indications: Pen G is not used as frequently
but still be effective against many Gram positive cocci such Streptococcus and some gram negatives such as Neisseria.
● Class: Penicillin derivative antibiotic containing a thiazoladine ring, a β lactam ring and side chains.
● Char: Broad spectrum antibiotic. Bactericidal. Resistance generally due to microorganism’s ability to produce β-lactamase enzyme and/or modifications of the PBP sites.
PO and IV. Rapid oral bioavailability. Distributed widely in all tissues except in the CSF.
Indications: Useful for urinary tract, ENT infections such as Strep throat and otitis media, lower respiratory, skin infections.
Side effects: GI, however generally less diarrhea than Ampicillin. Penicillin allergy and/ or anaphylaxis.
Amoxicillin and clavulanate/Augmentin
● Class: Penicillin derivative antibiotic containing Amoxil with clavulanic acid added to prevent β lactamase inhibition.
● MOA: Similar to Amoxil, binding to penicillin binding protein and inhibiting protein synthesis in the bacterial cell wall. Broader spectrum of activity yet with far less drug resistance.
Indications: Similar to amoxicillin especially when treating infections due to lactamase producing organisms.
!!! Side effects: Notable increased GI side effects from clavulanic acid. Clavulanate alone has very little antimicrobial activity. GI distress is common. Diarrhea very common. The most severe cause of antibiotic induced diarrhea is pseudomembranous colitis.
Amoxicillin and clavulanate/Augmentin DOSAGE
• Note that the 250 mg, 500 mg and 750 mg doses of Augmentin each have the same amount of clavulanate per dose, and that the differences in dosage only applies to the amount of Amoxicillin.
!!! In other words, two 250 mg Augmentin capsules will give you twice the clavulanate dose of one 500 mg Augmentin capsule.
• Cephalosporins are bactericidal and have the same mode of action as other beta- lactam antibiotics such as the penicillins.
• The cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls
The cephalosporins are divided intofive generations of drugs, based upon their spectrum of bacterial sensitivity.
• First-generation cephalosporins are predominantly active against Gram- positive bacteria (CEPH),
and successive generations have increased activity against Gram-negative bacteria, often with reduced activity against Gram-positive organisms. (CEF)
• Cephalexin/ Keflex***
• Cefazolin/ Ancef
• Cefaclor/ Ceclor
• Cefprozil/ Cefzil
• Cefixime/ Suprax
• Ceftriaxone/ Rocephin • Cefepime/ Maxipime
Class: Cephalosporin antibiotic, first generation.
MOA: Similar to penicillin with inhibition of protein synthesis of the bacterial cell wall via beta lactam activity.
Char: Broad spectrum coverage similar to that of Amoxil. Drug resistance generally occurs as a result of β-lactamase production or modifications of PBP.
contain Dihyrothiazolidine ring, β-lactam ring along with additional side chains.
Cephalexin/ Keflex Indications and SE
● Indications: ENT infections, bronchitis, skin infections. Varies with the generation of cephalosporin. Prophylaxis in surgery. Alternative to penicillins in allergic patients.
● Side effects: Similar to penicillin. GI effects such as diarrhea. Yeast overgrowth. Approximately 5%* of penicillin allergic patients will also be allergic to the cephalosporin class of drugs.
• activity stems from the presence of a large macrocyclic lactone ring.
• The mechanism is inhibition of bacterial protein biosynthesis by reversibly binding to the 50S subunit of the bacterial ribosome.
• This action is mainly bacteriostatic, but can also be bactericidal in higher concentrations.
• Macrolides tend to accumulate within leukocytes and are therefore actually transported into the site of infection.
• The primary means of acquired bacterial resistance to the macrolides occurs either by plasmid mediated changes or chromosomal mutation resulting in the inactivation of ribosomal response to the drug.
Post-transcriptional methylation of the 23S bacterial ribosomal RNA appears to be the main mode
• The antimicrobial spectrum of macrolides is similar to but slightly wider than that of penicillin, therefore drugs from the macrolide class are a common substitute for patients with a penicillin allergy.
• Beta-hemolytic Streptococci, Pneumococci, Staphylococci, and Enterococci are usually susceptible to Macrolides.
Unlike the penicillins, the macrolides have been shown to be effective against Chlamydia, Mycoplasma, Mycobacteria, and some Rickettsia.
• Erythromycin/ Erythromycin ***
• Azithromycin/ Zithromax
• Clarithromycin/ Biaxin
• Dirithromycin/ Dynabac
• Telirythromycin/ Ketec
• Lincomycin and Clindamycin are not Macrolides but are quite similar in structure and mechanism of action.
• Erythromycin is often used to treat respiratory tract infections because it covers typical organisms such as streptococcus and has better coverage of atypical organisms (such as Mycoplasma and Legionella).
• It is also used to treat Chlamydia, syphilis, and gonorrhea.
made from strain of the actinomycete Saccharopolyspora erythraea.
prevents bacteria from growing by interfering with protein synthesis.
• Erythromycin binds to the 23S RNA molecule in the 50S ribosome of susceptible bacteria.
• This ribosomal binding blocks the exit of the growing peptide chain halting bacterial replication.
Erythromycin MOA and SE
• Class: Macrolide antibiotic
• MOA: Inhibit protein synthesis by binding to 50 S bacterial ribosome.
• Char: Broad spectrum antibiotic that is generally bacteriostatic in low concentrations and bactericidal in high concentrations. May be used in penicillin allergic patients.
GI distress with upset stomach and N/V are very common occurrences with Erythromycin, especially if the drug taken without food. Most tablets are enteric coated in an effort to diminish upset stomach.
stevens johnson syndrome!
● Class: Macrolide antibiotic related to erythromycin, consisting of a many membered lactone ring.
● MOA: Inhibit protein synthesis by binding to 50 S bacterial ribosome.
● Char: Broad spectrum antibiotic that is generally bacteriostatic in low concentrations and bactericidal in high concentrations.
Char: Loading dose (500 mg to 1200 mg) speeds steady state - usually occurs by day 2. Widely distributed, except in the CSF. Long half-life (68 hours)
● Indications: Ear, nose and throat infections, sinusitis, bronchitis and pneumonia. Atypical infections such as Mycoplasma and Chlamydia infections. Long half-life and easy dosing schedule has made Zithromax one of most commonly used antibiotics.
SE: similar to erythromycin, less GI distress
The great popularity of Zithromax is due as much to it’s simple dosing schedule as it is to it’s anti-bacterial efficacy.
• A “Z-pack” is a prepackaged Rx of 6 tablets of Zithromax. Two tablets are taken on day 1, then I tablet per day on days 2 – 5.
• The long half-life of Azithromycin allows for drug levels to be maintained for twice the duration of the drug course.
• Tetracyclines are a group of broad spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance.
• This drug class is named for the four hydrocarbon rings structure.
• Tetracycline inhibits cell growth by inhibiting translation.
• It binds to the 16S part of the bacterial 30S ribosomal subunit.
• respiratory tract, sinuses, middle ear, urinary tract, intestines, and also gonorrhea, less effective than it once was due to development of resistance
• The most common current use : moderately severe acne and rosacea.
Tetra/doxycylines indications special
Doxycycline is also used as a prophylactic treatment for infection by Bacillus anthracis (anthrax) and is effective against Yersinia pestis, the infectious agent of bubonic plague.
• It is also used for malaria treatment and malaria prophylaxis.
• The tetracyclines are especially useful in patients allergic to both β-lactam drugs and macrolides.
Tetracyclines and kids
It is important to note that all of the tetracyclines can permanently stain teeth and as such should never be used in infants and children younger then age 8 or in pregnant women. (I personally wait to use a tetracycline until pt. is age 15 or older).
• Tetracyclines should not be given concurrently with calcium supplements or with dairy products as they are chelated by the drug and will markedly diminish drug absorption and bioavailability.
• Tetracycline/ Sumycin
• Doxycycline/ Doryx
• Minocycline/ Minocin
• Oxytetraccyline/ Terramycin
Class: Tetracycline antibiotic
MOA: Inhibits bacterial protein synthesis by interfering with 30 S ribosome. Bacteriostatic rather than bactericidal.
Indications: Effective in treating oral and respiratory infections caused by aerobic and anaerobic gram + and gram – organisms, killed by penicillins. Commonly used to treat acne and acne rosacea. Chlamydia. Lyme disease.
Rocky Mountain Spotted Fever.
SE:Chelates calcium ions. Accumulates in bone and teeth. Avoid taking this class of drugs with dairy products or calcium supplements.GI distress. Photosensitivity .
• Aminoglycosides are potent bactericidal antibiotics that work by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth.
• Aminoglycosides are useful primarily in infections involving aerobic, gram- negative bacteria such as Pseudomonas. Life threatening stuff!
The most frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia, complicated intra- abdominal infections, complicated urinary tract infections and nosocomial respiratory tract infections.
• Usually, once cultures of the causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics whenever possible.
• Gentamicin/ Garamycin ***
• Amikacin/ Amikin
• Kanamycin/ Kantrex
• Tobramycin/ Tobrex
Class: Aminoglycoside antibiotic
MOA: Binds to 30 S and 50 S ribosomal subunits interfering with protein synthesis. Bactericidal.
Indications: Primarily used to treat aerobic gram negative organisms. Useful in treating potentially life threatening infections such as meningitis, endocarditis or sepsis due to gram negative organisms. May also be used to treat Tuberculosis.
Char: No activity as an oral agent. Generally given IV when treating systemic infection. Often used with other antibiotics because of narrow spectrum of activity. Severe adverse effect profile. Used topically in the treatment of skin infections or infections of the eye.
● Side effects: Potentially nephrotoxic and ototoxic. These effects may be irreversible.
● Peak and trough blood levels of the drug must be checked during treatment.
• Quinolones and fluoroquinolones are synthetic bactericidal drugs
• Quinolones inhibit bacterial DNA gyrase, thereby inhibiting DNA replication and transcription.
• Quinolones can enter host cells easily and therefore are often used to treat intracellular pathogens such as Legionella and Mycoplasma.
- excellent, + good
gram negative--FIRST GENERATION (cino, acids)
gram positive--SECOND GENERATION (oxacins)
gram positive--SECOND GENERATION
• Ciprofloxacin/ Ciproxin***
• Cinoxacin/ Cinobac
• Lomefloxacin/ Maxaquin
• Norfloxacin/ Noroxin
• Ofloxacin / Floxin
• Levofloxacin/ Levaquin
• Sparfloxacin/ Zagam
• Gatifloxacin/ Tequin
• Moxifloxacin/ Avelox
• Trovafloxacin/ Trovan
● Class: Quinolone antibiotic (synthetic)
● MOA: Inhibits DNA gyrase, an enzyme responsible for properly uncoiling DNA during transcription.
● Urinary tract, ENT, upper and lower respiratory tract infections. Anthrax -
****ability to chelate calcium--like tetracyclines.dont take with Ca containing things
***avoid in under 12 kids, pregnancy, breast feeding
Char: Available as PO, IV and solution (for otitis externa and otitis media, conjucntivitis).
The Quinolones chelate calcium and can be deposited in cartilage, should be avoided in all children and infants and all pregnant and lactating females.
Side effects: Associated with increased risk for tendon injury (esp. Achilles tendon injury) in adults taking the drug. N/V, headache, insomnia, particularly in coffee drinkers. Ciproxin reduces the metabolic breakdown of caffeine, thus prolonging the effects.
• Class: Imidazole class of antibiotics
• Indication:Metronidazole has a spectrum of coverage that includes anaerobic bacteria and protozoa (giardia).Trichomonads, gram negative. Perforated bowel!!!
• MOA: Activated intermediates of the drug bind to DNA and inhibit further nucleic acid synthesis.
• Char: PO, topical gels and creams, parenteral form for I.V. administration.
Metronidazole/ Flagyl indications cont.
many, used commonly in practice:
• Vaginitis due to Trichomonas vaginalis (protozoal) as well as in their asymptomatic sexual contacts .
BV dt gardnarella infection
PID with other ABx
• As part of a multi-drug regimen directed at eradication of Helicobacter pylori in peptic ulcer disease.
Metronidazole is the drug of choice for first episodes of mild-to-moderate Clostridium difficile infection.
metronidazole /flagyl drug form
Metronidazole is a pro-drug
the therapeutic action of the drug occurs after the drug has been taken up by sensitive organisms such as anaerobic gram negative bacteria or Protozoa.
converted by redox enzyme pyruvate-ferredoxin oxidoreductase
Metronidazole/ Flagyl SE
• Side effects: oral Metronidazole therapy : upset stomach, nausea, vomiting, and diarrhea.
The sensation of a metallic taste in the mouth is another common complaint. Headaches. Thrush.
• Drinking alcohol while taking Metronidazole can result in a Disulfiram-like (aka Antabuse-like) reaction with nausea, vomiting, flushing, and tachycardia.
Metronidazole interrupts the etoh breakdown process by blocking the enzyme acetaldehyde dehydrogenase.
Consumption of alcohol should be avoided by all patients while taking oral Metronidazole and for at least 24 hours* after completion of the treatment course.
• Class: Nitrofuran antibacterial agent
• Indication: lower urinary tract infections ***
• MOA: Disrupts both DNA and RNA of
bacteria which are sensitive to the drug.
• Char: PO, IV, concentrated in the urine.
Indicated for lower UTI’s but not*** for pyelonephritis.
Considered safe for use in pregnancy prior to 38 wks of gestation. Resistance to other antibiotics has led to increased interest in Nitrofurantoin.
• The usual adult dose for a patient with uncomplicated cystitis is 100mg twice daily for 3, 5 or 7 days. Not recommended for use for pyelonephritis.
Nitrofurantoin/ Macrobid SE
• Side effects: nausea, vomiting, and diarrhea; less common reactions include fever and chills. Rare adverse effects include pulmonary fibrosis and drug-induced autoimmune hepatitis.
take away from food
• Clindamycin is a lincosamide antibiotic that is structurally similar to Lincomycin, from which it is derived.
• Clindamycin is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases such as malaria.
• It is also a common topical treatment for acne and can be useful against some strains of MRSA.
• Many species of streptococci (except for enterococci) and staphylococci are extremely susceptible. Most anaerobes, both gram-positive and gram-negative, are also susceptible.
Clindamycin/ Cleocin SE
GI upset, nausea, vomiting or diarrhea. Skin rashes, oral thrush and yeast vaginitis may occur. Pseudomembranous colitis from C. difficile overgrowth can occur.
• Class: Glycopeptide antibiotic
• Indication: Infections by *Gram-positive bacteria* which are unresponsive to other less toxic antibiotics. These are often severe or even life threatening infections.MRSA!!!!
• MOA: Inhibits synthesis of bacterial cell wall phospholipids as well as inhibition of peptidoglycan polymerization at a site separate from the penicillin binding proteins sites utilized by beta lactam antibiotics.
second line drug for outpatient C diff.
Vancomycin/ Vancocin resistance
• Vancomycin may still be effective in the treatment of infections due to Methicillin resistant Staph aureus (MRSA) however a culture and sensitivity is needed to rule out resistance to Vancomycin.
Vancomycin/ Vancocin route
• Char: Generally Vancomycin is often administered only by parenteral route (I.V.) because it is not absorbed orally.
• The only indication for oral administration of Vancomycin is the treatment of pseudomembranous colitis that is unresponsive to Metronidazole treatment or in cases in which there is a relapse of pseudomembranous colitis.
Vancomycin/ Vancocin SE
• Side effects: Vancomycin must be administered in a dilute solution over at least 60 minutes.
pain at the infusion site
red man syndrome or red neck syndrome.
• This syndrome, usually appearing within 5 to 10 minutes after start of the infusion
intense facial flushing, diffuse erythema and possible bullae formation and desquamation.
• Rifampicin is typically used to treat Mycobacterium infections, including tuberculosis and Hansen's disease (leprosy).
treatment of tuberculosis which may include Isoniazid, Pyrazinamide and/or Ethambutol as well as Streptomycin.
used as prophylactic therapy against *Neisseria meningitidis* (meningococcal) infection.
• Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells thus preventing transcription to RNA and subsequent translation
• ***The lipophilic nature of Rifampicin makes it a good candidate to treat the meningitis form of tuberculosis, which requires distribution to the CNS and penetration through the blood-brain barrier.
fever, gastrointestinal disturbances and rash.
• One of the most serious adverse effects is related to Rifampicin's hepatotoxicity and patients receiving Rifampicin should undergo baseline and frequent liver function tests to detect any signs of early liver damage.
body fluids can turn orange! harmless
• Rifaximin is a semi-synthetic antibiotic based on Rifamycin.
• It has poor oral bioavailability, meaning that very little of the drug will be absorbed into the blood stream when taken orally.
• Rifaximin is used in the treatment of traveler's diarrhea, irritable bowel syndrome, small intestine overgrowth syndrome and hepatic encephalopathy.
MOA: interferes with transcription by binding to the β-subunit of bacterial RNA polymerase. This results in the blockage of the translocation
Methicillin-resistant Staphylococcus aureus (MRSA)
• Methicillin-resistant Staphylococcus aureus (MRSA) (a.k.a. multidrug-resistant Staphylococcus aureus) is by definition any strain of Staph. aureus that is resistant to the beta-lactams, which include the penicillins and the cephalosporins.
• MRSA has evolved with the ability to survive treatment with beta-lactam antibiotics, including Methicillin, Dicloxacillin, Nafcillin, and Oxacillin.
initial pustule can look like a spider bite!
Methicillin-resistant Staphylococcus aureus (MRSA) treatment
Clindamycin, a Cephalosporin or a Fluoroquinolone are acceptable first line empiric choices for treating cellulitis.
New antibiotics (for MRSA)
• Daptomycin – for complicated skin and soft tissue infections
• Telavancin – for gram positive aerobes including MRSA
• Ceftaroline – skin and soft tissue infections including MRSA and for CAP except for MRSA related pneumonia
• Tigecycline – for gram positive and gram negative aerobes including MRSA.
• Linezolid for for gram positive and gram negative aerobes including MRSA.
Mupirocin / Bactroban MOA
• Mupirocin is an antibiotic originally isolated from Pseudomonas fluorescens.
• Mupirocin has a unique mechanism of action, which is selective binding to bacterial isoleucyl-tRNA synthetase, which halts the incorporation of isoleucine into bacterial proteins.
• Mupirocin is used topically, and is primarily effective against Gram-positive bacteria.
Mupirocin / Bactroban indications
fewer problems of antibiotic cross resistance.
• Mupirocin is indicated as a *topical treatment* for bacterial skin infections, such as impetigo, boils, and folliculitis.
Mupirocin is also indicated for open wounds at risk for infection or after incision and drainage procedures of skin abscesses.
Mupirocin remains an effective for MRSA.