Question | Answer |
Drugs used in UTIs | Trimethoprom+sulfamethoxazole
Fluorosuinolones
Antiseptics |
Trimethoprom+sulfamethoxazole | 1st choice for uncomplicated cystitis
Safe, effective, relatively inexpensive
Increasing drug resistance a problem |
Fluoroquinolones | Tend to be over used
Resistance developing
Still a good choice |
Antiseptics | Nitrofurantion
Useful in treating recurring UTIs |
Acute uncomplicated cystitis
Treatment | 3 day course of trimethoprim+sufamethoxazole
Increasing resistance of E.coli
If resistance is >20%, use Fluoro. |
Acute uncomplicated pyelonephritis or complicated UTIs
Treatment | Require longer Tx (7-14 days)
Sometimes with other drugs |
Sulfonamides
Clinical Uses | Single: Nocardiosis, Acute uncomplicated UTI
Combo prep: TMP/SMX
DoC for UTIs
Toxoplasmosis |
Sulfonamides
Oral Agents | Short acting: sulfisoxazole
Intermediate acting: sulfamethoxazole |
Sulfonamides
Topical agents | Opthalmic (bacterial conjunctivitis):
Sodium sulfacetamide
Burns: Silver sulfadiazine |
Sulfonamides
Mechanism of Action | Work as antimetabolites
Competitive inhibitors
-Structural analof or PABA
-Competes with PABA for dyhydropteroate synthetase
Essential for folate production |
Sulfonamides
Mechanism of Action
(cont) | Folic acid needed for nucleic acid synthesis
Bacteria cannon use exogenous folate
Must be made from PABA |
Sulfonamides
Resistance | Overproduction of PABA
Lower affinity of enzyme for drug
Decreased entry of drug
Resistance is increasing
Often resistant: -ococci |
Sulfonamides
Pharmacokinetics | Drug-Drug interactions:
Oral anticoagulants
Sulfonylurea hypoglycemic agents
Hydantion anticonvulsants
Effects potentiated by sulfa
Possible albumin displacement |
Sulfonamides
Adverse Effects
Urinary tract disturbances | Crystalluria, hematuria, obstruction
Rarely problem w/ newer drugs
Precipitates @ neutral/acidic pH
High doses/low fluid intake
Crystalluria: NaHCO3 |
Sulfonamides
Adverse Effects
Hematopoietic Disturbances | Acute hemolytic anemia:
Sensitization
*G6PD Deficiency*
Agranulocytosis:
Reversible |
Sulfonamides
Adverse Effects
Aplastic Anemia | Rare-direct myelotoxicity-can be fatal
Profound anemia, granulocytopenia and thrombocytopenia
Common with low bone marrow reserves (AIDS) |
Sulfonamides
Adverse Effects
Hypersensitivity reactions | More likely with longer acting agents
Any type reaction... Rash~3%
Rarely, potentially fatal, SJS |
Sulfonamides
Adverse Effects
Kernicterus | Increased risk if taken near end pregnancy
-Newborn and premature infants
-Avoid use in near term and nursing mothers
Causes encephalopathy |
Trimethoprim
Mechanism of Action | Antifolate
Synergistic sequential blockade
Competitive inhibitor of DHFR
Selective Toxicity |
Tripethoprim
Clinical Uses | Used in combo to treat several bacterial infxn
Single agent: approved primarily for UTIs
Initial Tx and prophylaxis
Used to treat prostatitis |
Trimethoprim
Resistance | Can result from:
Reduced cell permeability
Overexpression of DHFR
Altered DHFR with ↓ drug binding
**Most Common Mech** |
Trimethoprim
Adverse Effects | GI-NV
Dermatologic reactions
-Maculopapular rash, puritus
Folate deficiency impacting bone marrow |
Trimethoprim+Sulfamethoxazole
TMP/SMX
General | Fixed dose combo
-Synergistic
-aka Bactrim
Combo minimizes resistance
Combo usually bactericidal |
TMP/SMX
Clinical Uses
UTIs | Acute uncomplicated cystitis
Prolonged suppression of chronic UTIs and recurrent UTIs in females
Acute uncomplicated pyelonephritis in females
Useful in complicated UTIs |
TMP/SMX
Clinical Uses | Prostatis
Pneumocystis jiroveci pneumonia
-DoC for prophylaxis & Tx
Enterocolitis from Shigella
Traveler's diarrhea
-DoC for prophylaxis & Tx |
TMP/SMX
Clinical Uses
(cont) | Otitis Media
-Alt to amoxicillin
Respiratory Tract Infections
-H. influenzae |
TMP/SMX
Adverse Reactions | Those associated with TMP and SMX |
Fluoroquinolones | Ciprofloxacin
Levofloxacin
Moxifloxacin
Norfloxacin |
Fluoroquinolones
Spectrum of Action | Excellent G- activity
G+ activity depends on the drug
Includes MSSA and MRSA
H. influ, N. gonorrhea, Klebiella
Weak antipseudomonal activity
-Cipro has sig. pseudomonas |
Fluoroquinolones
Mechanism of Action | Block bacterial DNA synth
-Inhibits DNA gyrase and Topo IV
-Only drug class that inhibits DNA synth
Selective tox.
Bactericidal |
Fluoroquinolones
Ciprofloxacin | Active against G- including pseudomonas
G+ (MSSA), S.pneumoniae
N. gonorrhoeae
UTIs & systemic infxn
*First line for post anthrax* |
Fluoroquinolones
Levofloxacin | Expanded activity against G+ to include Strep. pneumoniae
Maintains activity against G- but only has weak pseudomonal activity |
Fluoroquinolones
Moxifloxacin | Similar spectrum as levo but includes:
E. faecalis
Anaerobes
Weak anti-pseudomonal activity |
Fluoroquinolones
*Clinical Activity* | UTIs including MDR bugs
Bacterial diarrhea
Infxn of soft tissues, bones & joints
Intra-abdominal and RTI including MDR bugs |
Fluoroquinolones
*Clinical Uses* | Post-inhalation exposure to anthrax
-Cipro
Upper and lower RTIs
-levo, moxi
-Cipro often effective, not DoC |
Fluoroquinolones
Resistance | ↑ problem from overuse
Mechanisms
-Change in drug binding region of enzyme
-Change in permeability of organism |
Fluoroquinolones
Pharmacokinetics | Well absorbed orally
-Antacids impair absorption
Norfloxacin
-Low serum levels (Tx of UTIs)
Most cleared renally
-Dose adjustment |
Fluoroquinolones
Adverse Effects | Extremely well tolerated
NV (most common)
*Achilles tendon rupture or tendinitis*
*QTc prolongation*
CNS: headache, dizziness |
Urinary Antiseptics | Oral agents with antibacterial activity in urine
-rapidly excreted
Use limited to UTIs
Prolonged suppression of bacteriuria |
Nitrofurantoin | Prevention of UTIs
Tx of uncomplicated UTIs
Chronic UTIs
Active against many strands of E.coli and entercocci
Used in pts with other allergies |
Nitrofurantoin
Mechanism of Action | Highly reactive species formed which damages DNA |
Nitrofurantoin
Spectrum of Activity | Many G+ and G-
Resistant species
-Most species of Pseudomonas & Proteus
-Many species of Enterobacter & Klebsiella |
Nitrofurantoin
Pharmacokinetics | Good oral absorption
Rapid metabolism and renal excretion
-No systemic ABx activity
-Only effective in urine
-Eliminated by GF and secretion |
Nitrofurantoin
Adverse Effects | NVD (most common)
Hypersensitivity Reactions
Hemolytic anemia in G6PD deficiency
Acute pneumonitis (elderly)
Urine turns a brown color |