Microbiology Antibiotics UWSOM

Trimethoprim/Sulfamethoxazole (oral)

Vancomycin (IV)

Cephalexin (oral)

Nafcillin (IV)

Penicillin

Isoniazid

Isoniazid + Rifampin + Pyrazinamide + Ethambutol

Amoxicillin

Amoxicillin/Clavulanate

Amoxicillin/Clavulanate

nitrofurantoin or trimethoprim/sulfamethoxazole

ceftriaxone + (azithromycin or doxycycline) [to cover Chlamydia]

(azithromycin or doxycycline) + ceftriaxone [to cover N. gonorrhoeae]

Penicillin

Beta lactam or doxycycline

Doxycycline

methicilin resistance (MRSA) and vancomycin resistance (VISA, VRSA)

penicillin resistance, multiple resistance

Vancomycin resistance (VRE) and multiple resistane

multiple resistance

rapid development of multiple resistance, carbapanemases.

Extended spectrum beta-lactamases, carbpenemases

Microorganism is inhibited or killed without harm to the host cells

Measure of the difference in effective dose relative to toxic dose

Range of organisms that are inhibited by a given agent

1) Beta lactam (cell wall synthesis
2) Macrolides (protein synthesis)
3) Fluoroquinolones (DNA synthesis)

Binds to peptides, prevent incorporation into chain

inhibits recycling of lipid carrier

Penicillins, Cephalosporins, Carbapenems, Monobactams, B-lactamase inhibitors

Act as structural analog of D-alanyl D-alanine. Prevent peptide-xlinking of peptidogylcan

Production of B-lactamase (acquired or inducible), production of altered penicillin binding proteins, impermeability and/or efflux (Pseudomonas)

Hypersensitivity: very safe in non sensitive individuals

Enzymes (carboxypeptidases, transpeptidases, endopeptidases) which normally function in synthesis and turnover of peptido. Binding to beta-lactam abx disrupts their normal function

Natural penicillins (gram + organisms), Penicillinase Resistant Penicillins (S. aureus - MRSA), Aminopenicillins (gram neg enteric), Penicillins against Pseudomonas, Penicillins combined with B-lactamase inhibitors

Effective against MRSA and penicillin resistant Strep pneumo.

Imipenem, meropenem, ertapenem, doripenem

broadest spectrum of all b-lactam abx, greatest resistance to bacterial b-lactamases, abx of last resort for serious gram neg infections such as extended spectrum beta-lactamase producing enteric bacteria

Production of penicillinase/beta lactamases, altered PBPs, and decreased permeability or active efflux

Staph aureus that have acquired resistance to beta-lactam class of abx through acquisition of a gene (mecA) encoding altered penicillin binding protein

1) acquired in hospital or other health care settings
2) bacteremia, sepsis, pneumonia, surgical site infection
3) strains likely to be resistant to other abx as well (tetracycline, macrolides, clindamycin)

1) infections in persons who have not been in a health care facility
2) skin infections most common
3) strains tend to be more virulent
4) strains tend to be more sensitive to other abx but trend is toward acquisition of additional resistance

used against multiple resistant staph (MRSA), enterococci, abx-associated colitis

IV, oral for abx-associated colitis

Binds to D-alanyl D-alanine of peptido subunit, prevents incorporation of subunit into glycan chain, prevents peptide x-linking

acquisition of genes encoding incorporation of D-lactate or serine instead of D-alanine at te terminal position of the pentapeptide - clinically imp in Enterococcus faecium

intermediate resistance (eg. staph aureus: VISA): thickening of peptido

VISA and some VRE

Phlebitis at site of infusion, neurotoxicity (hearing loss)

Telavancin: renal toxicity

Telavancin, Daptomycin, Linezolid

New abx class: cyclic lipopeptide

IV administration


Used for skin and subcutaneous infections caused by Gram-positive organisms (Staphylococcus including MRSA, Streptococcus, Entercoccus),
Staphylococcus aureus bacteremia, endocarditis

Poor penetration in lungs, inactivated by surfactant

Membrane depolarization, K+ efflux, rapid cell death

Thickening of peptidoglycan (Daptomycin-resistant strains also less sensitive to vancomycin (VISA))

Altered membrane lipid with increased positive charge

Mutations in transcriptional regulators and enzymes involved in phospholipid metabolism (E. faecium)

Muscle weakness and pain (increased creatinine phosphokinase levels)

Gastrointestinal disturbances

Broadest spectrum drug available against Gram-positives:
useful against MRSA, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci (VRE)

Inhibits protein synthesis by binding to 50S subunit, preventing formation of translation initiation complex

Mutations in 23S rRNA (rare)
Methylation of 23S rRNA (gene encoded on mobile genetic element)

myelosuppression (thrombocytopenia, anemia), gastrointestinal disturbance, neuropathy

Mupirocin
Linezolid
Aminoglycosides
Tetracyclines/Tigecycline
Chloramphenicol/Clindamycin/Retapamulin
Streptogramins
Macrolides

erythromycin, clarithromycin, azithromycin (Zithromax)

Oral and IV administration (clarithromycin oral only)


Useful for pneumonia, sinusitis, Chlamydia, Mycobacterium avium/intracellulare, Toxoplasma (protozoan parasite)

Blocks polypeptide exit tunnel in 50S ribosomal subunit, inhibits translocation

methylation of ribosomal RNA
efflux (seen is S. aureus)

gastrointestinal irritation

Anaerobic infections, community acquired MRSA

Administration: oral, IV, topical

Associate with 50S ribosomal subunit. Inhibits formation of peptide bonds.

methylation of rRNA (cross resistance with macrolides)

allergic reactions, diarrhea, antibiotic-associated colitis (toxin production by Clostridium difficile)

Streptogramins - quinoprinstin - dalfopristin


Bactericidal antibiotic for severe Gram-positive infections (MRSA, some Enterococcus)

Inhibits protein synthesis (interferes with tRNA translocation)

Synergistic binding of two components to 50S ribosome preventing peptidyl transfer, and blocking exit tunnel

Enzymatic inactivation
(lyase, acetyltransferase)

Arthralgia, myalgia (severe, limits use of this antibiotic)

Drug interactions

streptomycin, gentamicin, tobramycin, neomycin

Synergistic with ß-lactam antibiotics and vancomycin for serious Gram-positive infections

Useful against Pseudomonas aeruginosa

Inactive against anaerobes

Administration usually IV, monitoring of serum levels required
Aerosolized tobramycin used for cystic fibrosis patients

Bind to 30S and 50S ribosomal subunits, cause misreading of mRNA and premature release of ribosome

Production of aminoglycoside-modifying enzymes
Modification of outer membrane porins, efflux (P. aeruginosa)

renal, acoustic and vestibular, neuromuscular blockade

As a class, the most toxic of current widely used antibiotics

doxycycline, minocycline

Broad spectrum of activity

Effective for intracellular pathogens (e.g. Chlamydia trachomatis)

Oral administration

Bind to 30S ribosomal subunit, inhibit binding of aminoacyl tRNA to ribosome

active efflux from the bacterial cell, ribosomal protection

Hypersensitivity, discoloration of teeth in children, hepatotoxicity in pregnant women

structurally related to tetra

Broad spectrum of activity
Approved (2005) for skin and soft tissue infections (incl. MRSA), intra-abdominal infections, pneumonia. Use limited by low serum levels.

IV administration

Binds to 30S ribosomal subunit, inhibit binding of aminoacyl tRNA to ribosome (same as tetracyclines)

Efflux (rare)

Nausea, vomiting
FDA warns of increase in all-cause mortality associated with tigecycline treatment of serious infection (Sept., 2010)

Useful for eradication of nasal carriage of MRSA, treatment of skin infections caused by Staphylococcus aureus and Streptococcus pyogenes – topically applied

Inhibits protein synthesis by binding isoleucine-tRNA ligase, prevents protein synthesis by blocking incorporation of isoleucine in proteins

Acquisition of plasmd carrying gene encoding resisant target enzyme (mupA)
Resistance increasing among MRSA

occasional irrritation at site of administration

Fluoroquinolones
Rifampin
Fidaxomicin (2011)

Broad spectrum, expanding range of drugs in this class
3rd and 4th generation drugs require once daily dosing

Oral and IV administration

bind to DNA gyrase, topoisomerases, preventing DNA replication

mutations in DNA gyrase, topoisomerases

Efflux, target protection (plasmid mediated)

tendon rupture in adults, especially those over 60 years of age

mild gastrointestinal irritation

reversible joint toxicity in children

cardiac arrythmias

neuropathies

UTI, enteric infections, Pseudomonas aeruginosa

Useful only in prophylaxis or in combination

Important in treatment of tuberculosis

Prophylaxis of meningococcal disease

Oral and IV administration

Binds to bacterial RNA polymerase preventing the synthesis of RNA

mutation in RNA polymerase, occurs with high frequency

discoloration of urine, secretions

affects metabolism of other drugs - Cytochrome P450 induction

Rifaximin - non-absorbable version, intestinal infections

Effective for Clostridium difficile antibiotic-associated colitis

Oral administration, non-absorbable

Binds to bacterial RNA polymerase preventing the synthesis of RNA

mutation in RNA polymerase

mild toxicities

Metronidazole (Flagyl)
Nitrofurantoin

active against anaerobes and Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (protozoan parasites).

use limited to treatment and prophylaxis of urinary tract infections caused by E. coli

reactive intermediates damage DNA. Prodrug is reduced to short lived radical nitro anion.

mutations in reductases necessary for activation of the antibiotic

Sulfonamides, trimethoprim, trimethoprim sulfamethoxazole

structural analogs of para-amino benzoic acid, prevents bacterial synthesis of folic acid

structural analog of dihydrofolic acid, an intermediate in folate metabolism, and competitively inhibits the bacterial dihydrofolate reductase

Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci

Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci

Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci

An agent will stop the growth of a microorganism, but does not rapidly kill it.

rapid killing of the microbe

lowest concentration which will inhibit the growth of a specific microorganism

minimum bactericidal concentration

the effect is roughly the summation of the effects of each agent

the overall effect is less than the response of one of the agents used alone

the combination has an antimicrobial effect greater than the sum of the effects of each agent

Resistance to an antibiotic is a characteristic of the microbial species

Acquired by mutation, or introduction of a gene encoding resistance from another bacterial cell

Inactivation of the antibiotic
Decreased access of antibiotic to target
Alteration of the target