Abx Principles I Flashcards
Selection of abx therapy
- ID infecting organism
- Organism’s drug susceptibility
- Site of infection
- Patient factors
- Safety of antimicrobial agent
- Cost
ID Infecting organism
Gram Stain (Blood, serum, CSF, pleural fluid, synovial fluid, peritoneal fluid, urine)
Gram+ - PG cell wall layer –> Purple
Gram - Thin PC layer –> Pink
Common Gram + Cocci
STAPHYLOCOCCUS S. aureus S. epidermidis STREPTOCOCCUS S. pneumoniae S. pyogenes S. agalactiae ENTEROCOCCUS E. faecalis E. faecium
Common Gram + Bacilli
Listeria monocytogenes Corynebacterium Nocardia sp. Bacillus anthracis Clostridium sp.
Common Gram - Cocci/Coccobacilli
COCCI Neisseria meningitidis COCCOBACILLI Haemophilus influenza Moraxella catarrhalis
Common Gram - Bacilli (non-lactose fermenters)
Providencia stuartii Proteus mirabilis Pseudomonas aeruginosa Morganella morganii Actinobacter baumannii Stenotrophomonas maltophilia Burkholderia cepacia
Common Gram - Bacilli (lactose fermenters)
Escherichia coli Klebsiella spp Citrobacter spp Enterobacter spp Serratia marcescens
Culture to ID pathogen
R/O pathogenic vs. normal flora
Contaminant
Susceptibility Testing
Sensitivity to selected abx (MIC)
Minimum Inhibitory Concentration (MIC)
Lowest concentration of abx that prevents visible growth of organism in vitro
Quantitative value (micrograms/ml)
Bacteria is interpreted as susceptible (S), intermediate (I), resistant (R) to abx tested
Steps to Abx selection
- ID abx pathogen is susceptible to
- Check MIC (lower not necessarily better)
- Consider infection site/drug’s ability to reach site
- Consider abx’s PK/PD
- Make final decision based on pt specific factors (allergy, kidney fxn, comorbid conditions)
Minimum bactericidal concentration (MBC)
Lowest concentration of abx that will kill 99.9% of organisms in vitro rather than concentration that inhibits growth (MIC)
Rarely determined in clinical practice due to time and labor
Infection site
Empiric therapy –> organisms known to cause infection in question
Other influences of empiric therapy: patient factors, previous infections, recent travel history, place where infection acquired: Hospital, SNF, community
Narrow-spectrum abx
Poor for empiric therapy
Abx that acts on a single or limited group of microorganisms
(e.g. nafcillin and MSSA; isoniazid and Mycobacterium tuberculosis)
Extended-spectrum abx
Good for empiric therapy
Abx effective against GP organisms and significant # GN organisms
(e.g. ampicillin and amoxicillin)
Broad-spectrum abx
Excellent for Empiric Therapy
Abx that affect wide variety of microbial species
(e.g. quinolones, tetracycline, carbapenems)
MUST USE WITH CAUTION: altering normal bacterial flora can ppt superinfection from organisms like Clostridioides difficile or yeast
Combination Abx
Broaden abx coverage for empirical therapy (e.g. treat mixed infection w/ 2 abx to cover aerobic and anaerobic bacteria)
Achieve synergistic activity against known pathogen (e.g. nosocomial infection P. aeruginosa w/ two anti-pseudomonal abx; enterococcal endocarditis treated w/ combo of PCN abx and gentamicin)
Prevent emergence of resistance (Isoniazid and rifampin for TB)
RISKS: Superinfection, cost, drug toxicity
Empiric therapy once microbial results are known
Continue current abx therapy if appropriate based on C/S report
Narrow spectrum of coverage or # of abx to avoid risk of superinfection and drug resistance
Natural barriers to abx delivery
Capillary permeability may inhibit drug delivery in prostate, testes, eye, CNS, through placenta, blood brain barrier
Blood brain barrier
tight junctions of endothelium lining vessels at brain interface prevent large, non-lipid soluble stuff from crossing the basement membrane and entering the brain
Most abx cannot corss BBB unless…
brain becomes inflamed (e.g. meningitis) which allows abs to enter CSF
Abx characteristics determine empiric therapy
Lipid solubility (poor lipid solubility - beta-lactams)
ROA: Oral for mild infections/outpt
Parenteral admin for drugs poorly absorbed from GI tract/treatment of serious infections (e.g. oral vanco not absorbed)
Patient factors in abx selection
Immune system, kidney function, liver function, poor perfusion, age, pregnancy, allergies, risk factors for multi-drug resistant organisms
Patient Immune system factors in abx selection
INTACT IMMUNE SYSTEM REQUIRED TO ELIMINATE INFECTING ORGANISMS
Potenital immunocompromised pt: elderly, EtOH disorder, malnutrition, DM, HIV+, autoimmune disease, pregnancy, CA pt, transplant recipients, taking immunosuppressive meds
USE higher doses of bactericidal abx OR longer courses of treatment. AVOID bacteriostatic abx
Patient kidney function factors
Poor function may lead to accumulation abx and increase SE risk
Monitor Scr and CrCl to adjust abx therapy
Monitor drug levels w/ aminoglycosides and vancomycin to maximize therapy and avoid SE
Most common adjustment: keep dose (mg) same, extend dosing interval
Patient liver function factors
Avoid or reduce dose for abs eliminated by liver to reduce accumulation risk
(Erythromycin, clindamycin, metronidazole, rifampin)
Patient poor perfusion factors
Changes in peripheral blood make infections more difficult to treat (e.g. DM or PAD wounds)
Patient age factors
Selection of abx therapy (pathogen, formulation, taste!)
Abx dosing/organ function (neonates, elderly)
Patient pregnancy and breastfeeding factors
May require dosage increase d/t increased clearance (aminoglycosides, beta-lactams)
Many abx cross placenta and are expressed in breast milk
Category A abx risks
No human fetal risk or remote possibility of fetal harm
Category B abx risks
No controlled studies demonstrate human risk (or haven’t been conducted)
Animal studies do not demonstrate fetal risk or potential toxicity noted but not confirmed in controlled studies in women
(Beta-lactams, Clindamycin, erythromycin, azithromycin, metronidazole, nitrofurantoin, sulfonamides)
Category C abx risks
Animal fetal toxicity demonstrated
Human risk undefined d/t lack of controlled studies
DRUGS SHOULD ONLY BE GIVEN IF POTENTIAL BENEFIT JUSTIFIES POTENTIAL RISK TO FETUS
(Quinolones, Clarithromycin, Trimethoprim, TMP/Sulfa, Vanco, Gentamicin)
Category D abx risks
Positive evidence of human fetal risk, but benefits may outweigh risks
(Tetracyclines, aminoglycosides)
Category X abx risks
Human fetal risk clearly outweighs benefits
Contraindicated in women who are or may become pregnant
Patient allergy risk factors
Determine if allergy is true allergic reaction (rash, hives, SOB) or adverse effect (GI upset, sun sensitivity)
Risk factors for multidrug-resistant organisms
Prior abx therapy in past 90 days
Hospitalization > 2 days w/in last 90 days
Current hospitalization > 5 days
Immunosuppressive diseases or therapies
High frequency of resistance w/in community or institution (e.g. E. coli and UTIs)
General considerations in abx safety
Hypersensitivity/immune rxn: Urticaria - anaphylaxis (NEVER CHALLENGE documented SJS or toxic epidermal necrolysis rxns)
Patient ed: sx to look for and when to come in
Direct toxicity (high serum concentrations of Gent, Tob, Vanco directly affect host cellular processes causing toxicity)
Superinfections
Cost considerations in abx
Generic v. branded Formulation (tab/capsule v. suspension v. injectable v. ophth) Dose Therapy length # abx used
IV to PO abx switch
Oral is always cheaper
Convert when pt responding to therapy (feels better, sx improving)
One step closer to discharge
Ideal abx
Bacterial specificity Does not produce resistant strains Does not cause allergy/toxicity Does not cause other side effects Does not eliminate normal flora Cost effective Thus, ideal abx has not been found!!
Bacteriorstatic
Arrest growth/replication of bacteria
Limit spread until host’s immune system attacks, immobilizes, eliminates pathogen
(e.g. Tetracyclines, macrolides, sulfonamides, nitrofurantoin)
Bactericidal
Kill bacteria
Drugs of choice in seriously ill/immunocompromised patients
(e.g. beta-lactams, quinolones, glycopeptides, metronidazole, rifampin)
Concentration dependent killers
Rate of bacterial killing increases as drug concentration increases from 4 - 64 fold the MIC (Drug concentration / MIC)
e.g. AG, quinolones, daptomycin
Higher peak concentration of bactericidal abx, the faster the kill
1x/day dose and kills everything it contacts
Time-dependent killers
Efficacy is predicted by percentage of time that blood concentrations remain above MIC (Time>MIC)
(e.g. Beta-lactams, macrolids, clindamycin, vancomycin)
Bactericidal activity continues as long as serum concentration remains above MIC
Extended infusions (3-4 hrs) or continuous infusions (24 hours) kill more bacteria than intermittent dosing
Post-antibiotic effect
Persistent killing that occurs after abx levels have fallen below MIC
Allows less frequent abx dosing, decrease risk SE
(e.g. AG, quinolones, carbapenems, clindamycin, daptomycin)
Want to optimize dose of bactericidal abx to maximize AUC
Cell Wall Inhibitors
Compromise PG of cell wall
ABX THAT INHIBIT CELL WALL SYNTHESIS ONLY WORK ON ACTIVELY PROLIFERATING BACTERIA
Abx that inhibit cell wall synthesis are bactericidal
Examples of cell wall inhibitors
Beta-lactams: penicillins, cephalosporins, carbapenems, monobactams
Glycopeptides: Vancomycin, Daptomycin, Telavancin (ID specialists only)
Protein synthesis inhibitors
Target bacterial ribosomes to inhibit protein synthesis
Bacterial ribosome composed of 2 subunits: 30s, 50s
Some are bacteriostatic, some are bactericidal
Examples of protein synthesis inhibitors
Tetracycline (demeclocycline, doxycycline, minocycline, tetracycline)
Glycylcyclines (tigecycline)
Aminoglycosides (amikacin, gentamicin, tobramycin)
Macrolides (azithromycin, clarithromycin, erythromycin, telithromycin/ketek)
Macrocyclic (Fidaxomicin)
Clindamycin
Linezolid (zyvox)
Chloramphenicol
Quinupristin/Dalfopristin (synercid)
* - reserve for ID specialist
Nucleic Acid synthesis inhibitor
Inhibit DNA gyrase that relaxes DNA supercoil to promote strand breakage: quinolones (cipro-, levo-, moxi-floxacin)
Interfere in DNA synthesis: metronidazole
Interact w/ RNA polymerase to block RNA transcription: Rifampin
BACTERICIDAL
Folic acid antagonists
Enzymes used in synthesis of purines and pyrimidine (precursors of DNA/RNA) and other compounds needed for cellular growth and replication require folate-derived cofactors
Folic acid antagonist examples
Sulfamethoxazole (inhibits folate synthesis)
Trimethoprim (inhibits folate reduction)
TMP Sulfa –> always given together
Penicillins - ampicillin, amoxicillin, penicillin, dicloxacillin, augmentin, zosyn
Function: Cell wall inhibitors - only work on actively proliferating bacteria
Class: Beta-lactam
MOA: Bind and inactivate penicillin-binding proteins
Indication:GRAM POSITIVE, some gram negative; polymicrobial infections (used in combo w/ beta-lacatmase inhibitors), can be used narrow or broad spectrum for intra-abdominal, GYN, skin and soft tissue, respiratory infection (sinusitis and aspiration pneumonia), otitis media
Contraindications: n/a
Resistance/Interactions: 4 ways to break beta-lactam ring, change PBPs, changes porin so abx can’t get through, pump out abx when it does get in cell, cross allergic reactions with other beta-lactam antibiotics
Serious and common adverse effects: thrombocytopenia, leukopenia, interstitial nephritis, hypernatremia, hypersensitivity reacitons
Route/Pharmacokinetics: bactericidal, time dependent killing, IV, IM, PO, almost all are elimnated by kidneys, can’t cross BBB (poor lipid solubility)
Notes: Amoxicillin - commonly used for OM/URI - typically strep
Cephalosporins-cephalexin(1st gen), cefaclor (2nd gen)
Function: Cell wall inhibitors (bactericidal - as only work on actively proliferating bacteria)
Class: Beta-lactam antibiotic (largest class/family), ***BETA-LACTAMS ARE THE SAFEST FOR PREGNANCY OF ALL ANTIBIOTICS
MOA: bind to and inactivate penicillin-binding proteins
Indication: 1st gen: surgical prophylaxis, GP skin infxn, pneumococcal resp infxn, UTI; 2nd gen: CAP, skin infxn, other resp infxn, mixed aerobic/anaerobic infxn; 3rd gen: Same as 2nd + meningitis, nosocomial infxn; 4th gen: Best GN coverage; All cover Streptococcus and none cover Enterococcus
Contraindications: Allergy to PCNs
Resistance/Interactions: 4 ways to break beta-lactam ring, change PBPs, changes porin so abx can’t get through, pump out abx when it does get in cell, cross allergic reacitons with other beta-lactam antibiotics
Serious and common adverse effects: hypersensitivity reactions, hemolytic anemia, and interstitial nephritis
Route/Pharmacokinetics: bactericidal, time dependent killing - given more than once a day, poorly lipophilic, almost all are elimnated by kidneys (not ceftriaxone!), can’t cross BBB (poor lipide solubility)
Notes: CAN be used in meningitis as cephalosporins can cross BBB w/ inflammation (3rd gen)
Carbapenems (Meropenem, Ertapenem, Imipenem)
Function: Cell wall inhibitors (bactericidal - as only work on actively proliferating bacteria)
Class: Beta-lactam antibiotic
MOA: Bind and inactivate penicillin-binding proteins
Indication: MOST BROAD SPECTRUM OF ALL ABX skin, soft tissue, bone and joints, intra-abdominal, LRI, CNS infxn (Imipenem/meropenem). Most broad spectrum of all classes MSSA, Streptococcus, Pseudomonas, Acinetobacter, anaerobes (Ertapenem all these except no Pseudomonas or Ainetobacter coverage)
Contraindications:
Resistance/Interactions: Use with caution, last line of defense for highly resistant organisms. Can cause C. Diff infxn.
Serious and common adverse effects: neurotoxicity (seizures), C. diff infxns
Route/Pharmacokinetics: Eliminated by kidneys, require dosing adjustments for CKD. Imipenem and meropenem cross BBB. Ertapenem good for output tx (once daily dosing IV or IM)
Notes: New carbapenems:
Meropenem for complicated UTI w/ pyelonephritis caused by E. coli, Klebsiella pneumonia, and Enterbacter cloacae spp
Imipenem-cilastatin/relebactam (Recarbrio) for HABP/VABP, complicated UTI and complicated intra-abdominal infxns
Beta-lactamase inhibitor (sulbactam, clavulanate)
Function: Enzyme, not antibiotic
Class: Beta-lactamase inhibitor
MOA: Prevents degradation of beta-lactam abx
Indication: Always used in combo w/ other abx - penicillin; infections caused by gram - bacteria
Vancomycin
Function:Cell wall inhibitors (bactericidal - as only work on actively proliferating bacteria)
Class: Glycopeptide
MOA: inhibits phospholipids/peptidoglycan
Indication: GRAM POSITIVE - often saved for MRSA - MSSA, MRSA, MRSE, strep sp. Also after allergic reaction to beta-lactams, GI infections - c. diff, surgical prophylaxis in patients w/ prosthetic heart dz
Contraindications: pregnancy, class C
Resistance/Interactions: increasing resistance, now associated with staph aureus and enterococcus
Serious and common adverse effects: ototoxicity - may not be reversible, (tinnitus, vertigo) nephrotoxicity, red man syndrome if infused too quickly (not an allergic rxn)
Route/Pharmacokinetics: bactericidal, time dependent killing, given over 1-2 hours, IV/PO, cleared by the kidneys (watch trough levels. target: 10-20mcg/ml); dosing based on bodyweight (dose in mg) and kidney fxn. Loading dose: 25-30 mg/kg; Maintenance: 15-20 mg/kg every 12-48 hours
Notes: PO vanco - GI infections, IV vanco doesn’t get into GI tract, used more for MRSA, etc.
Aztreonam
Function: Cell wall inhibitors (bactericidal - as only work on actively proliferating bacteria)
Class: Monobactam
MOA: bind to and inactivate penicillin-binding proteins
Indication: GRAM NEGATIVE AEROBES ONLY, used for all UTIs, respiratory tract infecitons, pneumonia, bronchitis - safe to use when pt has allergy to PCN, cephs, and carbapenems - reserve for these patients
Contraindications:
Resistance/Interactions:
Serious and common adverse effects:
Route/Pharmacokinetics: eliminated by kidneys - dosage adjustment with CKD
Notes: Safe to use in pt w/ PCN, ceph, carbapenem allergy so reserve for these pt
Gentamicin, Tobramycin, Amikacin
Function: Inhibit protein synthesis (bacteriostatic and bacteriocidal)
Class: Aminoglycosides
MOA: Enter via porin channels in outer membrane, bind 30s subunit to interfere w/ protein synthesis (Bactericidal w/ concentration dependent killing and significant post abx effect)
Indication: serious bacteremias due to GN organisms (monotherapy not recommended unless treating UTI)
Spectrum: aerobic GN bacilli - pseudomonas, klebsiella, serratia, Proteus, E. coli, Acinetobacter, Enterobacter.
Gent (syn w/ beta-lactam to treat strep, staph and enterococcus). Tob (more active against pseudomonas than gent). Amikacin (reserve for resistant pseudomonas and acinetobacter infections)
Contraindications: pregnancy - all class D but gentamicin, caution with peds or elderly
Resistance/Interactions: Efflux pumps, decreased uptake and/or modification and inactivation by plasmid-associated synthesis of enzymes specific for only 1 AG (Due to different chem structures, cross-resistance between AG cannot be presumed); AMIKACIN resistant to many enzymes that inactivate Gent and Tob so RESERVE FOR RESISTANT PATHOGENS
Serious and common adverse effects: Ototoxicity (vestibular/auditory) directly related to high peak levels and LOT >5 day; Nephrotoxicity w/ high trough levels; Avoid using w/ other drugs w/ similar SE (e.g. loop diuretics)
Route/Pharmacokinetics: 5-7 mg/kg initial dose, obtain drug level 6-14 hours post infusion, further dosing based on nomogram (Traditional dosing for peds, pregnant, burn, CF, neutropenic, CKD pt). Synergy dosing 1mg/kg q8hr.
Notes:
Clindamycin
Function: Inhibit protein synthesis (bacteriostatic and bacteriocidal)
Class: Lincosamide (only in this class)
MOA: Irreversible binding to 50S ribosomal subunit/inhibit protein synthesis
Indication: aspiration pneumonia, URIs (esp in PCN allergic pt), surgical prophylaxis in pt allergic to Bacteroides spp.
Spectrum: Gram+, anaerobes, Strep. spp., MSSA, MRSA (CA), anaeobes
Contraindications:
Resistance/Interactions: Efflux pumps, decreased uptake and/or modification and inactivation by plasmid-associated synthesis of enzymes ; C. diff now resistant to clindamycin & beginning to see resistance to Bacteroides spp.
Serious and common adverse effects: NV, D d/t to C. diff, skin rash, pseudomembranosus colitis from C. diff overgrowth/megacolon
Route/Pharmacokinetics: Eliminated in bile, hepatic dysfunction requires dosage adjustment
Notes:
Linezolid
Function: Inhibit protein synthesis
Class: Oxazolidinone (first abx in this brand new class)
MOA: Binds to 50S ribosomal subunit/inhibit protein synthesis; bactericidal time-dependent killing, PAE 3-6 hours
Indication: complicated skin and skin structure infections, nosocomial and CAP, MRSA and VRE infxns ID USE ONLY
Spectrum: Gram+ ONLY! MRSA, VRE, penicillin-resistant streptococci
Contraindications:
Resistance/Interactions:
Serious and common adverse effects: NVD, HA, rash, taste perversion, thrombocytopenia, anemia, leukopenia, risk of serotonin syndrome (weak selective MAO activity, can occur if taken w/ an SSRI. RARELY: optic neuritis, peripheral neuropathies with LOT > 28 days
Route/Pharmacokinetics: No adjustments for hepatic/renal dysfnxn.
Notes:
Doxycycline, Monocycline (long acting)
Demeclocycline, Tetracycline (short acting)
Function: Inhibit protein synthesis
Class: Tetracyclines
MOA: Reversibly binds 30S subunit to inhibit protein synthesis (BACTERIOSTATIC w/ PAE)
Indication: acne, STIs, Doxy: Lyme Disease, Rocky mountain spotted fever, cholera, Doxyk: atypical bacteria (Mycoplasma, Legionella, Chlamydia) ass. w/ CAP; Doxy - sclerosing agent for pleurodesis
Spectrum: BROAD - Gram+ (MSSA, MRSA) and Gram-, protozoa, spirochetes, mycobacteria, chlamydia, mycoplasma, atypical species
Contraindications: Avoid w/ dairy products (decreases absorption)
Resistance/Interactions: efflux pump that expels drug from cell, proteins that interfere w/ binding to ribosome, enzymatic inactivation (resistance to one TCN doesn’t mean resistance to all)
Serious and common adverse effects: NVD, epigastric distress (minimize by taking w/ food), hepatotoxicity, photosensitivity, dizziness, vertigo, tinnitus; Avoid in kids < 8yo and during pregnancy/breastfeeding. Binds to tissues undergoing calcification (permanent teeth discoloration, temporary growth stunting in kids)
Route/Pharmacokinetics: Adjust dose for CKD (Doxy eliminated in bile bur no dosage adjustment required). Drug interactions: Ca, Fe, Mg, Zn, oral contraceptives, warfarin, phenytoin, carbamazepine
Notes:
Lefamulin (NEW abx)
Function: Inhibit protein synthesis
Class: Pleuromutilin
MOA: Binds 50S subunit
Indication: CAP
Contraindications: pregnancy? (causes fetal harm in animal studies)
Resistance/Interactions:
Serious and common adverse effects: QT interval prolongation. CYP3A4 inducers decrease effectiveness and CYP3A4 inhibitors increase SE risk
Route/Pharmacokinetics: Oral: 600mg q12hr/5-7 days; IV: 150mg q12hr
Notes:
Ciprofloxacin, Levofloxacin, Moxifloxacin, Delafloxacin (NEW)
Function: DNA Synthesis Inhibitor
Class: Quinolone
MOA: inhibit DNA gyrase and bacterial topoisomerase IV that promotes DNA strand breakage. PAE 1-6 hrs.
Indication: see individual cards
Contraindications: caution in peds, pregnancy class C
Resistance/Interactions: increasing resistance against Staphylococcus, Pseudomonas, Serratia via efflux pumps, mutations to DNA gyrase and topoisomerase IV
Potent CYP1A2 inhibitors so Significant interaction w/ warfarin, theophylline!!
Serious and common adverse effects: GI (NV, C. diff diarrhea), CNS (HA, dizziness, lower seizure threshhold, peripheral neuropathy), Skin (photosensitivity, rash, SJS), Endocrine (hyper or hypo-glycemia), Renal (interstitial nephritis), Cardiac (QT prolongation, aortic rupture/tear), Other: arthropathy, tendonitis, tendon rupture*
* - FDA black box warning
Route/Pharmacokinetics: reduction required for Cipro and Levo in pt w/ renal dysfunction; Moxifloxacin eliminated by liver; Avoid giving w/ divalent ions (Ca++, Fe++, Mg++, Zn++) due to binding/decrease GI absorption;
Notes:
Ciprofloxacin Spectrum/Indications
Spectrum: Gram- bacilli, Pseudomonas, atypicals
NO ANAEROBIC OR GRAM+ coverage
Indications: UTIs, Pseudonomal PNA, acute diarrheal illness, anthrax
Levofloxacin Spectrum/Indications
Spectrum: MSSA, Streptococcus spp., Gram- bacilli, atypicals, Pseudomonas
RESPIRATORY QUINOLONE
Indications: CAP, URIs, prostatitis, UTIs, skin and soft tissue infxn, nosocomial PNA
Moxifloxacin Spectrum/Indications
Spectrum: MSSA, Streptococcus spp., anaerobes, atypicals
RESPIRATORY QUINOLONE
Indications: CAP, URIs NOT UTIs (processed outside of kidney/urinary system! Eliminated by liver)
Delafloxacin Spectrum/Indications
Spectrum: Gram + (S. aureus including MSSA and MRSA, Streptococcus spp., Enterococcus faecalis)
Gram- (E. coli, Enterobacter, Klebsiella, Pseudomonas aeruginosa)
Indications: acture bacterial skin and skin structure infxns
REQUIRES DOSING ADJUSTMENTS FOR KIDNEY DYSFXN
Metronidazole (Flagyl)
Function: DNA synthesis inhibitor
Class:
MOA: binds cellular proteins and DNA to inhibit protein synthesis (BACTERICIDAL TIME DEPENDENT)
Indication: intra-abdominal infxn, C. diff colitis, giardiasis, amebiasis, trichmoniasis, bacterial vaginosis, acne (topical)
Spectrum: Giardia, Trichomonas, anaerobic cocci, anaerobic GN bacilli (Bateroides fragilis), C. diff
Contraindications: EtOH (drinking, hand sanitizer, hair spray etc.)
Resistance/Interactions:
Serious and common adverse effects: NV, epigastric distress, HA, unpleasant metallic taste, dark urine, peripheral neuropathy, dysarthria, thrush
POTENTIAL FOR DISULFIRAM RXNS (severe NV) in PRESENCE OF ALCOHOL (hair spray, hand sanitizer, etc.)
Route/Pharmacokinetics: Metabolized by liver (adjust dose for pt w/ severe liver disease); Drug and metabolite excreted in urine (adjust dose for pt w/ renal dysfxn); CYP3A4 inhibitor (interacts w/ warfarin, phenytoin, phenobarb, rifampin
Notes:
Trimethoprim-Sulfamethoxazole (TMP-SMZ)
Function: Folic acid antagonists
Class:
MOA: Inhibits folate synthesis needed for protein synthesis and growth (TMP-Sulfa is synergistic, enhancing activity of both drugs)
Indication: skin and soft tissue infxns, UTI, prostatitis, salmonella, shigellosis, URIs, Pneumocystis jirovecii pneumonia (PCP)
Spectrum: MSSA, MRSA (CA), Toxoplasma gondii, Gram- bacilli, Pneumocystis jirovecii
Contraindications: CrCl<15; Pregnancy class C
Resistance/Interactions: Random mutations and plasmid transfers, efflux pumps; Increasing resistance to E. coli and MSSA
Serious and common adverse effects: Skin (rash, photosensitivity, SJS, TEN), GI (NV), Kidney (interstitial nephritis, urolithiasis, crystalluria w/ azotemia), Other (thrombocytopenia, leukopenia, hepatitis, hyperkalemia, fever, vasculitis)
Route/Pharmacokinetics: dosage reductions required in pt w/ CKD; avoid if CrCl < 15ml/min; avoid in severe hepatic dysfxn; Interacts w/ warfarin, phenytoin, hypoglycemic agents, methotrexate
Notes:
Nitrofurantoin
Function: Inhibit protein synthesis
Class:
MOA: Poorly understood but inhibits protein synthesis
Indication: uncomplicated UTIs; Suppress bacteremia, lack systemic abx effects d/t rapid metabolism and excretion in urine. CAN BE USED FOR UTI PROPHYLAXIS
Spectrum: Gram+ and Gram-, specifically E. coli, Citrobacter, E. faecium, E. faecalis, S. saprophyticus
Contraindications: CrCl<60, Women >/= 38 weeks pregnant (to avoid hemolytic anemia in neonate)
Resistance/Interactions: resistance to complicated UTIs
Serious and common adverse effects: NV, anorexia, pulmonary fibrosis (w/ chronic use), hemolytic anemia (w/ G6PD deficiency), neuropathies, skin rash, photosensitivity
Route/Pharmacokinetics: BACTERIOSTATIC and rapidly metabolized (doesn’t enter blood or concentrates in kidneys) avoid if CrCl < 60
Notes:
URI pathogens
CA S. pneumoniae H. influenzae Moraxella catarrhalis Group A strep
CA LRI pathogens
S. pneumoniae H. influenzae M. catarrhalis Klebsiella pneumonia Mycoplasma pneumoniae C. pneuomoniae viruses
Aspiration LRI pathogens
Mouth flora (aerobic and anaerobic)
HA LRI pathogens
S. aureus (including MRSA)
P. aeruginosa
other Gram- aerobic bacilli
HIV coinfected RI pathogens
Pneumocystis jiroveci
S. pneumoniae
Brain/meningitis pathogens in <2 mo
E. coli
Group B Strep
Listeria monocytogenes
Brain/meningitis pathogens in 2mo - 12yo
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae
CA Brain/meningitis pathogens in adults
S. pneumoniae
N. meningitidis
HA Brain/meningitis pathogens in adults
S. pneumoniae
N. meningitidis
Gram- aerobic bacilli
HIV coinfected brain/meningitis pathogens
Cryptococcus neoformans
S. pneumoniae
CA UTI pathogens
E. coli
Enterococcus spp.
Staphylococcus saprophyticus
other Gram- aerobic bacilli
HA UTI pathogens
E. coli
other Gram- aerobic bacilli
Enterococcus spp.
Skin/soft tissue pathogens
Staphyloccus spp.
Streptococcus spp.
Gram- aerobic bacilli
Anaerobes in wounds/decubital ulcers
Intestinal pathogens
Campylobacter Salmonella Shigella E. Coli H. pylori in stomach
Rifampin
Function:
Class: Rifamycin (structurally similar to macrolides)
MOA: Inhibits DNA dependent RNA polymerase to block RNA transcription
Indication: TB, used w/ cell wall active agent to treat serious GP infxn (MRSA) that fail to respond to other abx treatments, post-exposure meningitis prophylaxis
Spectrum: GP cocci, moderate activity against GN bacilli (N. meningitidis, N. gonorrhoeaee, H. influenza), M. tuberculosis
Contraindications:
Resistance/Interactions: POTENT ENZYME INDUCER/INCREASES METABOLISM OF MANY DRUGS (antiarrhymics, azole antifungal drugs, clarithromycin, estrogens, statins, warfarin, HIV meds)
Serious and common adverse effects: NVD, HA, fever, anemia, thrombocytopenia, hepatotoxicity (monitor LFTs); CHANGE bodily fluids to orange-red color
Route/Pharmacokinetics:
Notes:
