Microbiology- Antimicrobials Flashcards
Antimicrobial therapy Imagen
Pag. 187
Penicillin G, V
- Mechanism
- Clinical Use
Penicillin G (IV and IM form), penicillin V (oral). Prototype β-lactam antibiotics.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces). Also used for gram ⊝ cocci (mainly N meningitidis) and spirochetes (namely T pallidum). Bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊝ cocci, and spirochetes.
Penicillin G, V
- Adverse effects
- Resistance
Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia, drug-induced interstitial nephritis.
β-lactamase cleaves the β-lactam ring. Mutations in penicillin-binding proteins.
Penicillinase-sensitive penicillins
(Amoxicillin, ampicillin; aminopenicillins.)
- Mechanism
- Clinical Use
Same as penicillin. penicillinase sensitive. Also combine with clavulanic acid
“HHELPSS”
Extended-spectrum penicillin—H influenzae, H pylori, E coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
*AmOxicillin has greater Oral bioavailability than ampicillin.
Penicillinase-sensitive penicillins
- Adverse effects
- Resistance
Hypersensitivity reactions, rash, pseudomembranous colitis.
Penicillinase (a type of β-lactamase) cleaves β-lactam ring.
Penicillinase-resistant penicillins (Dicloxacillin, nafcillin, oxacillin.) - Mechanism - Clinical Use - Adverse effects - Resistance
Same as penicillin.
S aureus (except MRSA).
Hypersensitivity reactions, interstitial nephritis.
MRSA has altered penicillin-binding protein target site.
Antipseudomonal penicillins (Piperacillin, ticarcillin) - Mechanism - Clinical Use - Adverse effects
Same as penicillin
Pseudomonas spp. and gram ⊝ rods.
Hypersensitivity reactions.
β-lactamase inhibitors
CAST.
Clavulanic acid, Avibactam, Sulbactam, Tazobactam.
Cephalosporins
- Mechanism
- Organisms not covered
- Adverse effects
- Resistance
β-lactam drugs that inhibit cell wall synthesis
LAME:
Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Low rate of crossreactivity even in penicillin-allergic patients. nephrotoxicity of aminoglycosides.
Inactivated by cephalosporinases. Structural change in penicillinbinding proteins (transpeptidases).
Cephalosporins 1st Generation
- Names
- Clinical use
cefazolin, cephalexin
PEcK.
gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella
pneumoniae. Cefazolin used prior to surgery to
prevent S aureus wound infections.
Cephalosporins 2nd Generation
- Names
- Clinical use
cefaclor, cefoxitin, cefuroxime, cefotetan
HENS PEcK.
gram ⊕ cocci, H influenzae, Enterobacter aerogenes, Neisseria spp., Serratia marcescens, Proteus mirabilis, E coli, Klebsiella pneumoniae.
Cephalosporins 3rd Generation
- Names
- Clinical use
ceftriaxone, cefotaxime, cefpodoxime, ceftazidime
serious gram ⊝ infections resistant to other β-lactams.
Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease.
Ceftazidime—Pseudomonas.
*Can cross blood-brain barrier.
Cephalosporins 4th Generation
- Names
- Clinical use
Cefepime
gram ⊝ organisms, with activity against Pseudomonas and gram ⊕ organisms.
Cephalosporins 5th Generation
- Names
- Clinical use
Ceftaroline
broad gram ⊕ and gram ⊝ organism coverage;
unlike 1st–4th generation cephalosporins, ceftaroline covers Listeria, MRSA, and Enterococcus faecalis—
does not cover Pseudomonas.
Carbapenems
- Names
- Mechanism
DIME
Doripenem, Imipenem, Meropenem, Ertapenem
Imipenem is a broad-spectrum, β-lactamase– resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I)
Newer carbapenems include ertapenem (limited
Pseudomonas coverage) and doripenem.
Carbapenems
- Clinical use
- Adverse effects
Gram ⊕ cocci, gram ⊝ rods, and anaerobes. limit use to life-threatening infections or after other drugs have failed.
Meropenem has a risk of seizures and is stable to
dehydropeptidase I.
GI distress, rash, and CNS toxicity (seizures) at high plasma levels.
Monobactams (Aztreonam)
- Mechanism
- Clinical use
- Adverse effects
Less susceptible to β-lactamases. Synergistic with aminoglycosides. No cross-allergenicity with penicillins.
Gram ⊝ rods only—no activity against gram ⊕ rods or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.
Usually nontoxic; occasional GI upset.
Vancomycin
- Mechanism
- Clinical use
Inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors. Bactericidal against most bacteria (bacteriostatic against C difficile).
Gram ⊕ bugs only—serious, multidrug-resistant organisms, including MRSA, S epidermidis, sensitive Enterococcus species, and Clostridium difficile (oral dose for pseudomembranous colitis).
Vancomycin
- Adverse effects
- Resistance
NOT
Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing—red man syndrome (largely preventable by pretreatment with antihistamines and slow infusion rate), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
(eg, Enterococcus) via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac.
Protein synthesis inhibitors
All are bacteriostatic, except aminoglycosides
(bactericidal) and linezolid (variable).
“Buy AT 30, CCEL (sell) at 50.”
30S inhibitors
Aminoglycosides
Tetracyclines
50S inhibitors
Chloramphenicol, Clindamycin
Erythromycin (macrolides)
Linezolid
Aminoglycosides
- Names
- Clinical uses
GNATS: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin.
*Require O2 for uptake; therefore ineffective against anaerobes.
Severe gram ⊝ rod infections. Synergistic with β-lactam antibiotics. Neomycin for bowel surgery.
Aminoglycosides
- Adverse effects
- Resistance
Nephrotoxicity, Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics). Teratogen.
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
Tetracyclines
- Names
- Characteristics
- Clinical uses
Tetracycline, doxycycline, minocycline.
Limited CNS penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take
tetracyclines with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut.
Borrelia burgdorferi, M pneumoniae. Drugs’ ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia. Also used to treat acne. Doxycycline effective against MRSA.
Tetracyclines
- Adverse effects
- Resistance
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.
uptake or efflux out of bacterial cells by plasmid-encoded transport pumps.
Glycylcyclines (Tigecycline)
- Mechanism
- Clinical use
- Adverse effects
Binds to 30S. Generally bacteriostatic.
Broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage. Multidrug-resistant organisms (MRSA, VRE) or infections requiring deep tissue penetration.
GI symptoms: nausea, vomiting.
Chloramphenicol
- Clinical use
- Adverse effects
- Resistance
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and rickettsial diseases. Limited use due to toxicity
Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature
infants because they lack liver UDP glucuronosyltransferase).
Plasmid-encoded acetyltransferase inactivates the drug.
Clindamycin
- Clinical use
- Adverse effects
Anaerobic infections (eg, Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive group A streptococcal infection.
*Treats anaerobic infections above the diaphragm vs metronidazole below
Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea.
Oxazolidinones (Linezolid)
- Clinical use
- Adverse effects
- Resistance
Gram ⊕ species including MRSA and VRE.
Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome.
Point mutation of ribosomal RNA.
Macrolides (Azithromycin, clarithromycin, erythromycin)
- Clinical use
- Adverse effects
- Resistance
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram ⊕ cocci (streptococcal infections in patients allergic to penicillin), and B pertussis.
MACRO: gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsinophilia.
Methylation of 23S rRNA-binding site prevents binding of drug.
Polymyxins (Colistin (polymyxin E), polymyxin B)
- Mechanism
- Clinical use
- Adverse effects
Cation polypeptides that bind to phospholipids on cell membrane of gram ⊝ bacteria. Disrupt cell membrane integrity leakage of cellular components cell death.
Salvage therapy for multidrug-resistant gram ⊝ bacteria (eg, P aeruginosa, E coli, K pneumoniae). Polymyxin B is a component of a triple antibiotic ointment used for superficial skin infections.
Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory failure.
Sulfonamides
- Names
- Mechanism
- Clinical use
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine.
Inhibit dihydropteroate synthase, thus inhibiting folate synthesis. Bacteriostatic (bactericidal when combined with trimethoprim).
Gram ⊕, gram ⊝, Nocardia. TMP-SMX for simple UTI.
Sulfonamides
- Adverse effects
- Resistance
Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, Stevens-Johnson syndrome, kernicterus in infants, displace
other drugs from albumin (eg, warfarin).
Altered enzyme (bacterial dihydropteroate synthase), Lower uptake, or High PABA synthesis.
Dapsone
- Mechanism
- Clinical use
- Adverse effects
Similar to sulfonamides
Leprosy (lepromatous and tuberculoid), Pneumocystis jirovecii prophylaxis.
Hemolysis if G6PD deficient, methemoglobinemia.
Trimethoprim
Inhibits bacterial dihydrofolate reductase. Bacteriostatic
Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.
Megaloblastic anemia, leukopenia, granulocytopenia, which may be avoided with coadministration of folinic acid. TMP Treats Marrow Poorly.
Fluoroquinolones
- Names
- Mechanism
- Clinical use
Ciprofloxacin, enoxacin, norfloxacin, ofloxacin; respiratory fluoroquinolones—gemifloxacin, levofloxacin, moxifloxacin.
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. Bactericidal. Must not be taken with antacids.
Gram ⊝ rods of urinary and GI tracts (including Pseudomonas), some gram ⊕ organisms, otitis externa.
Fluoroquinolones
- Adverse effects
- Resistance
GI upset, superinfections, skin rashes, headache, dizziness. Less commonly, can cause leg cramps and myalgias.
Contraindicated in pregnant women, nursing mothers, and children < 18 years old due to possible damage to cartilage. Some may prolong QT interval.
May cause tendonitis or tendon rupture in people > 60 years old and in patients taking prednisone. Ciprofloxacin inhibits cytochrome P-450.
Fluoroquinolones
- Resistance
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Daptomycin
- Mechanism
- Clinical use
- Adverse effects
Lipopeptide that disrupts cell membranes of gram ⊕ cocci by creating transmembrane channels.
S aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE. Not used for pneumonia (avidly binds to and is inactivated by surfactant).
Myopathy, rhabdomyolysis.
Metronidazole
- Mechanism
- Clinical use
- Adverse effects
Forms toxic free radical metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
GET GAP on the METRO: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C difficile).
Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache, metallic taste.
Antimicrobial prophylaxis
- High risk for endocarditis and undergoing surgical or dental procedures
- Exposure to gonorrhea
- History of recurrent UTIs
- Exposure to meningococcal infection
- Pregnant woman carrying group B strep
- Amoxicillin
- Ceftriaxone
- TMP-SMX
- Ceftriaxone, ciprofloxacin, or rifampin
- Intrapartum penicillin G or ampicillin
Antimicrobial prophylaxis
- Prevention of gonococcal conjunctivitis in newborn
- Prevention of postsurgical infection due to S aureus
- Prophylaxis of strep pharyngitis in child with prior rheumatic fever.
- Exposure to syphilis
- Erythromycin ointment on eyes
- Cefazolin
- Benzathine penicillin G or oral penicillin V
- Benzathine penicillin G
Treatment of highly resistant bacteria
- MRSA:
- VRE:
- Multidrug-resistant P aeruginosa, multidrug-resistant Acinetobacter baumannii:
vancomycin, daptomycin, linezolid, tigecycline, ceftaroline, doxycycline.
linezolid and streptogramins (quinupristin, dalfopristin).
polymyxins B and E (colistin).
Prophylaxis in HIV patients
- CD4 < 200 cells/mm3
- CD4 < 100 cells/mm3
- CD4 < 50 cells/mm3
- TMP-SMX Pneumocystis pneumonia
- TMP-SMX Pneumocystis pneumonia and toxoplasmosis
- Azithromycin or clarithromycin Mycobacterium avium complex.
