Antibacterials Flashcards
Beta lactamase inhibitors
Clavulanic Acid, Sulbactam, Tazobactam, Avibactam
DOC for syphilis and Rheumatic fever prophylaxis
benzathine penicillin G
- lasts for 3-4 weeks
- given IM
Drug less active against Gram neg and given orally
Penicillin V
Drug of choice for:
• Strep throat
Penicillin V
Employed mostly orally for mild-moderate infections eg,
pharyngitis, tonsilitis, skin infections (caused by
Strep)
Restricted to treatment of b-lactamase-producing
staphylococci
Nafcillin, Oxacillin, Dicloxacillin
- b-lactamase resistant
Used for treatment of a number of infections: acute otitis media, streptococcal pharyngitis, pneumonia, skin infections, UTIs etc.
• Widely used to treat upper respiratory infections
Safe in pregnancy and children
Amoxicillin
prophylactic treatment for dog, cat, and human bites - immediate
Amoxicillin + clavulanic acid
prophylactic treatment for dog, cat, and human bites - a week or more
Ampicillin + sulbactam
Ampicillin used for same things as amoxicillin
Commonly used to treat Pseudomonas aeruginosa
Main clinical use = as an injectable treatment of Gram
negatives
Ticarcillin, Piperacillin
Which penicillin is safe to give to a patient with kidney failure
Nafcillin
- bc excreted in bile
Which penicillin causes maculopapular rash
Ampicillin and amoxicillin
Which penicillin causes pseudomembranous colitis
Ampicillin
Which penicillin causes interstitial nephritis
Methicillin
Which penicillin causes neutropenia
Nafcillin
Which penicillin causes hepatitis
Oxacillin
Which penicillin causes positive combs test
Penicillin G and V
less susceptible to beta-lactamases. Rarely need to combine with a beta-lactamase inhibitor
Cephalosporins
All cephalosporins are inactive against ?
LAME
listeria, legionella, acinetobacter, mycoplasma, enterocci
Which cephalosporin generation is active against MRSA
5th
DOC for surgical prophylaxis
1st gen cephalosporins —> cephazolin
*from gen 1-3 gram pos activity decreases
* first gens are Cefazolin, Cephalexin
prophylaxis & therapy of abdominal and pelvic cavity infections
Cefotetan & cefoxitin
* second gen cephalosporins are Cefaclor, Cefoxitin, Cefotetan, Cefamandole
DOC for gonorrhea
Ceftriaxone
* 3rd gen cephalosporins—> Ceftriaxone, Cefoperazone, Cefotaxime, Ceftazidime,
Cefixime
Prophylaxis of meningitis in exposed individuals
Ceftriaxone and vancomycin
Treatment of disseminated Lyme disease (CNS or
joint infection)
Ceftriaxone
Cephalosporins that have action against P.aeruginosa
Cefoperazone, Ceftazidime
Treatment of complicated UTI’s, complicated intra-abdominal infections, febrile neutropenia
Wide antibacterial spectrum eg, enterobacter,
Haemophilis, Neisseria, E.coli, pneumococci, P.mirabilis & P.aeruginosa
Cefipime
*4th gen cephalosporins (broad spectrum)
Treatment for Skin and soft tissue infection due to MRSA, particularly if Gram-negative pathogens are coinfecting
Ceftaroline
*5th gen
Cephalosporins are eliminated via kidney except
ceftriaxone & cefoperazone excreted in bile
Which drug AE is kernicterus
Ceftriaxone
Cefamandole, cefoperazone & cefotetan contain
methyl-thiotetrazole group, all can cause
hypoprothrombinemia and disulfiram- like reactions
Prevent by k1 admin and avoiding alcohol
Which carbapenem is less broad and not active against P.aeruginosa
Ertapenem
* DIME: Doripenem, Imipenem, meropenem, Ertapenem
- generally broad spectrum
Imipenem forms potentially nephrotoxic metabolite. Combine with what to prevent toxicity ?
Cilastatin
Active against Aerobic Gram-negative rods ONLY (including pseudomonas)
Aztreonam - monobactam
- resistant to beta lactamases
Useful for treatment of Gram-negative infections in
patients allergic to penicillin
Aztreonam
Bacterial glycoprotein
Active against Gram-positive bacteria only
Effective against multi-drug resistant organisms (eg,
MRSA, enterococci, PRSP)
Vancomycin
- can give if patient allergic to penicillin
Binds to the D-Ala-D-Ala terminus of nascent
peptidoglycan pentapeptide
Vancomycin
Given orally (and Drug of Choice) for the treatment of
staphylococcal enterocolitis or antibiotic-associated
pseudomembranous colitis (C.difficile)
Vancomycin
Which drug causes red man or red neck syndrome ?
Vancomycin
- infusion-related flushing over face and upper torso
AE of vancomycin
Ototoxicity (drug accumulation)
• Nephrotoxicity (drug accumulation)
• DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome
Effective against resistant Gram-positive organisms
(eg, MRSA, enterococci, VRE & VRSA)
Treatment of complicated skin/structure infections
caused by susceptible S.aureus
Daptomycin
This drug AE is Elevated creatine phosphokinases (recommended to discontinue coadmin. of statins)
Daptomycin
Marked nephrotoxicity → mainly topical use
Bacitracin
Bind reversibly to 30S subunit of ribosome, preventing attachment of aminoacyl tRNA
Tetracyclines
Drugs of choice for:
• Chlamydia
• Mycoplasma pneumoniae
• Lyme disease
• Cholera
• Anthrax prophylaxis
• Rickettsia (Rocky Mountain Spotted Fever,
typhus)
Tetracyclines
Tetracyclines are excrete in urine except
doxycycline
- through bile
Discoloration & hypoplasia of teeth, stunting of
growth (generally avoided in pregnancy & not given in
children under 8y)
TERATOGENIC – all cross placenta & are excreted into
breast milk (FDA category D)
Photosensitization
Tetracyclines
Generally used to treat complicated skin, soft tissue and intraabdominal infections. Increased risk of mortality has been observed compared with other antibiotics when used to treat serious infections
Tigecycline- glycylcyclines
Glycylcycline Contraindications
Pregnancy & children <8y
This drug only requires once daily dosing
Aminoglycosides
** Amikacin, Gentamicin, Tobramycin, Streptomycin,
Neomycin
Concentration-dependent killing
aminoglycosides
Time-dependent killing
penicillins, cephalosporins
Covalently bind to 30S ribosomal subunit prior to
ribosome formation leading to irreversible inhibition of initiation complex :
• misreading of mRNA, &
• blockade of translocation
Aminoglycosides
Aminoglycosides resistance
Inactivated by acetylation, phosphorylation and adenylation
Drugs of choice for:
• Empiric therapy of infective endocarditis
Gentomycin and vancomycin
AE OF AMINOGLYCOSIDES
Ototoxicity
• Nephrotoxicity
• Neuromuscular blockade (myasthenia gravis =
contraindicated)
• Pregnancy (contraindicated unless benefits outweigh risks – FDA Category D)
Used as adjunct in treatment for hepatic
encephalopathy
Oral neomycin
- reduces gut flora to reduce the nitrogen containing compounds that can cross the BBB
Other alternatives
• Lactulose
• Oral vancomycin
• Oral metronidazole
• Rifaximin
Who traps NH4 in colon effectively reducing
plasma ammonia concentrations
Lactulose
Reversibly bind to the 23S rRNA of the 50S subunit
blocking translocation
Macrolides
- Erythromycin, Clarithromycin, Azithromycin
- mainly treats gram pos infections
- bacteriostatic
DOC for whooping cough (B.pertussis)
Erythromycin
These macrolides inhibit CYP450
Erythromycin & clarithromycin
inhibit protein synthesis in mitochondrial ribosomes
→ bone marrow toxicity
Very broad spectrum
Chloramphenicol
Inhibits hepatic oxidases (3A4 & 2C9)
Chloramphenicol
Drug causes bone marrow depression and Gray baby syndrome (cyanosis)
Chloramphenicol
Number 1 drug for Potentially fatal pseudomembranous colitis (superinfection of C.difficile)
Clindamycin
- ampicillin also causes this problem
treatment of infections caused by drugresistant Staphylococci or VRE
Streptogramins
Quinupristin, Dalfopristin
Inhibitors of CYP 3A4
Streptogramin
Oral bioavailability 100%
Linezolid
Cannot combine linezolid with
antidepressants
- non selective inhibitor of MAO
- like SSRIs bc it is a weak reversible inhibitor of MAO
- can lead to serotonin syndrome
Only treats C. difficile
Fidaxomicin
Antibiotic belonging to monoxycarbolic acid class
• Activity against most Gram-positive cocci, including
MRSA and most streptococci (but not enterococci)
Mupirocin
How is mupirocin given
Intranasal:
• Eradication of nasal colonization with MRSA in
adult patients and healthcare workers
• Topically:
• Treatment of impetigo or secondary infected
traumatic skin lesions
Fluoroquinolones
Second generation
Ciprofloxacin
Third generation
Levofloxacin
Fourth generation
Gemifloxacin, Moxifloxacin
Inhibit bacterial DNA replication via interference with
topoisomerase II (DNA gyrase) & IV
Fluoroquinolones
Gram -ve activity with some activity against Gram +ve and atypical organisms.
Synergistic with b-lactams
Ciprofloxacin
Expanded Gram -ve activity
Improved activity against Gram +ve and atypical organisms. Excellent activity against S.pneumoniae
Levofloxacin
Improved Gram +ve activity and anaerobic activity
Moxifloxacin and Gemifloxacin
Travelers diarrhea
P.aeruginosa (CF patients)
Prophylaxis against meningitis
(alternative to ceftriaxone & rifampin)
Ciprofloxacin
2nd gen
Prostatitis
STD’s (not syphilis)
Skin infections
Acute sinusitis, bronchitis, TB
Community acquired pneumonia
Levofloxacin
3rd gen
Community acquired pneumonia
Moxifloxacin and gemifloxacin
Fluoroquinolones AE
Connective tissue problems (avoid in pregnancy,
nursing mother, under 18’s) – Black Box Warning!
• Peripheral neuropathy (FDA warning)
• QT prolongation (moxifloxacin, gemifloxacin,
levofloxacin)
• High risk of causing superinfections (C.difficile, C
albicans, streptococci)
Inhibit bacterial folic acid synthesis
• Synthetic analogs of PABA (p-amino-benzoic acid)
• Competitive inhibitors (& substrate) of dihydropteroate synthase
Sulfonamides
Sulfamethoxazole, Sulfadiazine, Sulfisoxazole
Sulfonamides AE
Crystalluria (nephrotoxicity)
• Hypersensitivity reactions
• Hematopoietic disturbances (esp. patients with G6PD deficiency)
• Kernicterus (in newborns and infants <2 months)
** Ceftriaxone (2nd gen cephalosporins also causes kernicterus)
inhibitor of bacterial dihydrofolate reductase
Trimethoprim
Drug used for
- UTI’s
- Bacterial prostatitis
- Bacterial vaginitis
Antifolate effects (contraindicated in pregnancy)
Trimethoprim
Combination of trimethoprim & sulfamethoxazole
Cotrimoxazole
Synergistic: inhibition of sequential steps in
tetrahydrofolic acid synthesis
Uncomplicated UTI’s (drug of choice)
Cotrimoxazole
PCP (drug of choice)
Nocardiosis (drug of choice)
Toxoplasmosis (alternative drug)
Cotrimoxazole
Contraindicated in pregnancy (esp. 1st trimester)
Cotrimoxazole
Anaerobic conditions are vital for optimal activity
• Undergoes reductive bioactivation of its nitro group by ferredoxin
• Forms cytotoxic products that interfere with nucleic acid synthesis → damage DNA
Metronidazole
Metronidazole AE
Disulfiram-like effect (avoid alcohol)
Headache, dark coloration of urine, metallic taste
Not advised in 1st trimester
Blocks transcription by binding to b subunit of bacterial DNA-dependent RNA polymerase
→ leading to inhibition of RNA synthesis
Rifampin
Patient not responding to vancomycin to treat mycobacteri. What to use ?
Rifampin
Rifampin resistance
Point mutations in rpoB, the gene for the b subunit of RNA polymerase
→ decreased affinity of bacterial DNA-dependent RNA polymerase for drug
• Decreased permeability
Treatment for
- TB
• Prophylaxis for individuals exposed to meningitis
• Prophylaxis in contacts of children with H.influenzae
type B
• MRSA (with vancomycin)
Rifampin
Imparts harmless orange/red color to bodily fluids
• Strongly induces most CYP P450 isoforms
• SAFE IN PREGNANCY
Rifampin AE
Attach to and disrupt bacterial cell membranes
Also, bind to and inactivate endotoxin
Gram-positive bacteria are resistant
Extremely nephrotoxic
Polymyxin B
This drug is contraindicated in patients with
- Significant renal insufficiency
• Pregnancy at term (38-42 weeks)
• Infants <1 month (risk of hemolytic anemia)
Nitrofurantoin
- may cause hemolytic anemia (G6PD deficient patients)
What is the empiric antibacterial treatment for infective endocarditis?
Vancomycin and gentamicin (due to emergence of
MRSA and penicillin-resistant streptococci)
When can Rifampin be added to empiric antibacterial treatment for infective endocarditis?
In the presence of a prosthetic heart valve.
Linezolid or daptomycin are options for patients with
intolerance to vancomycin of resistant organisms.
What is the antibacterial treatment for infective
endocarditis caused by a-hemolytic streptococci?
Penicillins (penicillin G and ampicillin) often in
combination with gentamicin.
