Antibacterials Flashcards
Natural Penicillins:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Minimal
Inhibitors of cell wall synthesis
Streptococcus #Enterococcus (esp E. faecalis)
Treponema pallidum
(Syphilis)
#Mouth anaerobes
#Hypersensitivity #Seizures (high doses)
-Have lost utility against
Staphylococci (due to β-lactamase)
-Only cidal against Enterococcus when combined with aminoglycoside
- Streptococcus spp. are uniformly susceptible, with exception of some S pneumoniae isolates
Aminopenicillins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Ampicillin/Amoxicillin
Inhibitors of cell wall synthesis
Streptococcus
Enterococcus (espE. faecalis)
Listeria monocytogenes
Escherichia.coli, Proteus mirabilis, Haemophilus influenzae (but resistance is common due to B-lactamase)
Treponema pallidum
(Syphilis)
#Lyme
#Hypersensitivity #Seizures (high doses)
Aminopenicillins + Beta-lactamase Inhibitors:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Ampicillin+ Sulbactam
Amoxicillin+Clavulanate
Inhibitors of cell wall synthesis
Streptococcus
Enterococcus (espE. faecalis)
methicillin-sensitive Staphylococcus
aureus (MSSA)
Escherichia.coli, Proteus mirabilis, Haemophilus influenzae (but resistance is common due to B-lactamase)
B-lactamase producing strains of H. influenzae, some strains of Klebsiella spp., E coli.
Treponema pallidum
(Syphilis)
#Lyme
Excellent anaerobic activity (including Bacteroides fragilis)
#Hypersensitivity #Seizures (high doses) #Diarrhea
Penicillinase Resistant Penicillins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Nafcillin/Oxacillin
Dicloxacillin
Inhibitors of cell wall synthesis
EXCELLENT MSSA (drugs of
choice)
Streptococcus
#Hypersensitivity #Seizures (high doses) Hepatotoxicity (oxacillin) and interstitial nephritis (nafcillin)
- “Penicillinase” is β-lactamase that hydroyzes penicillins but not these agents
- Unique due to hepatic elimination, so no dosing adjustments necessary in renal insufficiency
Extended Spectrum Penicillin + Beta-lactamase Inhibitor:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Ticarcillin+Clavulanate
Piperacillin+Tazobactam
Inhibitors of cell wall synthesis
EXCELLENT MSSA (drugs of
choice)
Streptococcus
Enterococcus (esp E. faecalis)
Broad-spectrum activity, including Pseudomonas
Treponema pallidum
(Syphilis)
Mouth anaerobes
Excellent anaerobic activity (including Bacteroides fragilis)
#Hypersensitivity #Seizures (high doses) #Diarrhea
1st Generation Cephalosporins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
oral anaerobes
Cefazolin
Cephalexin
Cefadroxil
Inhibitors of cell wall synthesis
MSSA
Streptococcus
E. coli, Klebsiella
#Hypersensitivity #Seizures (high doses)
Uses: skin and soft tissue infections
2nd Generation Cephalosporins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Cefuroxime
Cefaclor
Cefprozil
*Cefoxitin
Inhibitors of cell wall synthesis
MSSA, Streptococci
- Poor MSSA
- Streptococcus
E. coli, Klebsiella
H. influenzae
#oral anaerobes *Moderate B. fragilis
#Hypersensitivity #Seizures (high doses)
3rd Generation Cephalosporins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
oral anaerobes
Ceftibuten Cefdinir Cefpodoxime Ceftriaxone Cefotaxime Cefixime *Ceftazidime **Ceftaroline
Inhibitors of cell wall synthesis
MSSA
Streptococcus
*Poor MSSA, Streptococcus
**Only β-lactam with activity against MRSA, excellent against Streptococcus
Broad, not Pseudomonas
- Broad, including Pseudomonas
- *Broad, not Pseudomonas
#Hypersensitivity #Seizures (high doses)
#Ceftriaxone unique for non-renal elimination #Ceftriaxone/cefotaxime gold- standard for community-acquired meningitis, N. gonorrhea, neuro Lyme
4th Generation Cephalosporins:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
None
Cefepime
Inhibitors of cell wall synthesis
MSSA
Streptococcus
Broad activity , including Pseudomonas
#Hypersensitivity #Seizures (high doses)
Monobactams:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Aztreonam
Inhibitors of cell wall synthesis
None
Good, including Pseudomonas
#Hypersensitivity #Seizures (high doses)
Safe to use in patients with severe allergic reactions to other beta- lactams (like penicillin)
Carbapenems:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Imipenem/Cilastatin
Meropenem
Doripenem
*Ertapenem
Inhibitors of cell wall synthesis
Streptococcus
MSSA
Enterococcus faecalis
*No Enterococcus
Excellent, including Pseudomonas
*Doesn’t cover Pseudomonas
Anaerobes, including excellent B. fragilis
#Hypersensitivity #Seizures (high doses) Imipenem- ↑ incidence of seizures in pts with ↓ renal function & or hx of seizures
Glycopeptide:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Vancomycin
Inhibitors of cell wall synthesis
Streptococcus
MRSA/MRSE
Enterococcus
Not VRE
C. difficile
Rash and hypotension with rapid IV administration (Red Man’s syndrome)
Nephrotoxicity (mostly with high doses or in combination with aminoglycosides)
Neutropenia, allergy (rare)
Used exclusively for gram- positive infections (IV) and C. difficile-associated diarrhea (PO)
- Old drug, but resistance amongst staph/strep is rare
- At UPMC, ~80% of Enterococcus faecium is VRE (vancomycin- resistant), as is ~20% of E. faecalis
Fosfomycin:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Inhibitors of cell wall synthesis
Streptococcus
Staphylococcus
Enterococcus
E. coli & others
Not pseudomonas
- Only available in USA as single- dose oral regimen for acute cystitis in females
- First line option due to increasing E coli resistance to other agents (TMP/SMX, quinolones)
TMP/SXM:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Inhibitors of DNA & RNA synthesis
S. aureus
S. epi
Most MRSA & MRSE
Poor streptococcus
Most gram- including Stenotrophomonas maltophilia
EXCEPT
Pseudomonas
Nocardia
Pneumocystis jiroveci (PCP) (fungus)
Toxoplasma gondii (protozoa) NOT
B. fragilis or other anaerobes
- Skin rash (3-4%): from mild reactions that resolve with continuation to Stevens-Johnson (rare)
- Renal: TMP inhibits secretion of creatinine and may lead to mild (~10%) elevations of serum creatinine
- Hyperkalemia
- Acute tubular necrosis
- Acute interstitial nephritis
- Hematological: neutropenia, thrombocytopenia (rare)
- Many uses, including urinary tract, gastrointestinal, skin, pneumocystis (both treatment and prophylaxis), toxoplasmosis, nocardiosis
- Monitor for increase in INR when used concomitantly with warfarin (drug interaction)
- Dosing based on Trimethoprim component
Rifampin:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Inhibitors of DNA & RNA synthesis
Staph/Strep
No enterococcus
Not used as monotherapy
N. meningitidis (prophylaxis only)
M. tuberculosis
- Orange-red discoloration of tears, sweat, urine, etc
- Gastrointestinal
- Hepatotoxicity: from mild, transient elevations in bilirubin to fulminant hepatitis (rare)
- MANY drug-drug interactions
- Utilized almost exclusively in combination due to rapid emergence of resistance when utilized alone
- Uses: Tuberculosis, staphylococcal endocarditis, infections of prosthetic materials
Fidaxomicin:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Inhibitors of DNA & RNA synthesis
Streptococcus
Staphylococcus
Enterococcus
Gram-positive anaerobes (especially C. difficile)
Only use is for C. difficile infection
Quinolones:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Ciprofloxacin
Levofloxacin
*Moxifloxacin
Inhibitors of DNA & RNA synthesis
Streptococcus
S. pneumo (Moxi > Levo > Cipro)
Poor enterococcus
No Staph
Cipro/Levo: Excellent activity against most (incl Pseudomonas)
Moxi: Moderate activity, poor activity vs. Pseudomonas
- Most have poor anaerobic activity
- Moxi- has ↑ activity,
including Bacteroides fragilis - Good activity atypicals: Chlamydia spp. Mycoplasma
Legionella spp - CNS: headache, dizziness, insomnia, mood alterations, seizures
- Tendinitis with rupture (especially achilles tendon in elderly patients corticosteroids) - Prolonged QTc
- C difficile: although possible with all antibiotics, FQ portend especially high risk
Cipro & Levo adjusted for renal pts, Moxi not adjusted
Aminoglycosides:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Gentamicin
Tobramycin
Amikacin
Inhibitors of protein synthesis
Enterococcus
Streptococcus
Staphylococcus
Broad, including Pseudomonas (ami > tobra > genta)
- Nephrotoxicity- via proximal tubular cell accumulation. Usually reversible
- Ototoxicity (rare)- Usually irreversible
- Almost always used in combination:
- -> With cell-wall active agents for staph/strep/enterococcal endocarditis
- -> As “double-coverage” for severe gram-negative infections until susceptibility known
- Pharmacokinetic monitoring necessary to maximize efficacy (high peaks) and minimize toxicity (low troughs)
Macrolides:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Azithromycin
Clarithromycin
Inhibitors of protein synthesis
Strep pneumoniae & other strep
MSSA
H. influenzae N. gonorrhea M. catarrhalis Campylobacter H. pylori
- Atypicals: Legionella, Mycoplasma, Chlamydia
- Anaerobic activity but NOT B. fragilis
- Mycobacterium avium complex (MAC)
- Erythromycin utilized for pro- kinetic gastrointestinal effects. Clarithro/Azithro have fewer GI side effects.
- Torsades de pointes (ventricular tachycardia) associated with clarithromycin, mostly when utilized in combination with interacting agents (via CYP3A4 hepatic enzymes; azithromycin is not metabolized via this process)
- Utilized for coverage of atypical pathogens in community-acquired pneumonia
- Also utilized for otitis, sinusitis, pneumonia
- Clarithromycin: More prone to
drug-drug interactions - Clarithromycin: non-buterculous mycobacterial infections, combination therapy for H. pylori
- Azithromycin: chlamydial infections, traveler’s diarrhea, MAC prophylaxis in AIDS
Tetracyclines:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Tetracycline
Doxycycline
Minocycline
Inhibitors of protein synthesis
Strep pneumoniae
Staphlococcus (incluidng MRSA)
Enterococcus
Strep pyogenes
H. influenzae
N. gonorrhea
M. catarrhalis
Campylobacter
Anaerobes, atypicals, Rickettsial infections, Lyme disease
- GI, esophageal ulceration (take
with fluid and remain upright) - Gray-brown to yellow
discoloration of teeth in children - Photosensitivity
- Appropriate for a wide variety of infections, although use in the hospital is generally limited due to alternative agents with more potent gram-negative activity
- May still be options for COPD exacerbations, outpatient treatment of upper respiratory tract infections
Glycylcyclines:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Tigecycline
Inhibitors of protein synthesis
Extensive, including MRSA, VRE
Extensive, although no Pseudomonas
Extensive anaerobic coverage, including Bacteroides fragilis
- GI, esophageal ulceration (take with fluid and remain upright) - Gray-brown to yellow discoloration of teeth in children - Photosensitivity - Nausea & vomiting
Not appropriate for treatment of bacteremia due to low serum levels
Lincosamides:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
Clindamycin
Inhibitors of protein synthesis
S. aureus (including MRSA)
S. epi
Streptococcus
Not enterococcus
Good anaerobic activity, but resistance common with Bacteroides
- Nausea/vomiting/diarrhea
- C. difficile colitis (Can occur with any antibiotic, but most
commonly associated with clindamycin)
Due to risk for C. difficile, should
be rarely utilized:
- oral infections and skin and soft
tissue infections in patients with penicillin allergy
- As part of combination therapy in necrotizing fasciitis (Gp A Strep)
Oxazolidinone:
Drug(s)
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
Negligible
Linezolid
Inhibitors of protein synthesis
Vast activity, even against MRSA and most VRE (vancomycin- resistant Enterococcus)
- Myelosuppression, mostly thrombocytopenia, common with treatment courses >2 weeks
- Reversible MAO-I and can cause serotonin syndrome when given in combination with other serotonergic agents
Mainly reserved for patients with resistant gram-positive infections (esp VRE & MRSA) with few other options
Nitrofurantoin:
Mechanism of Action
Gram+
Gram-
Other
Adverse Effects
Comments
None
DNA damaging agents
Most gram+ including VRE
Most E. coli, Klebsiella, Enterobacter (Proteus and Pseudomonas almost always resistant)
- Gastrointestinal (lower with
macrocrystalline formulation- due to slower dissolution) - Pulmonary: wide range, from acute cough and dyspnea to fibrosis with chronic use
Only utilized for treatment of urinary tract infections but NOT pyelonephritis
