• They treat parasitic and fungal infections (and bacterial, in the case of TMP-SMX)
• They are broad-spectrum, bacteriostatic agents (but over the years, E. coli has become more resistant to T-SMX)

Interfere with bacterial synthesis of folic acid through competitive inhibition of dihydropterate synthetase. Ultimately leads to inhibition of DNA synthesis in susceptible organisms.

Enzyme is responsible for incorporating para-aminobenzoic acid (PABA) into dihydrofolic acid. This blocks the synthesis of dihydrofolic acid which subsequently leads to a decreased amount of tetrahydrofolic acid (a cofactor necessary for the synthesis of purines, thymidine, and DNA) thus inhibiting cell growth.

Inhibiting folate synthesis in people is an adverse effect.

• Good oral bioavailability (fair amount of the drug ends up in the circulatory system)
• Peak plasma concentration reached in 2 - 3 hours

• Readily pass into most body fluids.
• Varying degrees of plasma protein binding (only free, unbound drug can be considered active)
• Variably reach CSF (highest levels attained with sulfadiazine)
• Getting to the site of the infection is only one of the requirements; then, it must cover the organism you are trying to treat.

• Hepatically metabolized by acetylation and glucuronidation (liver).
• Not a lot of liver-related reactions. Not 100% metabolized (most drugs aren’t). Some eliminated by the kidney.

• Both parent drug and metabolites are primarily eliminated by the kidney
• Older compounds may crystallize in acidic urine. This can be minimized with high fluid intake. Counsel patient to hydrate as much as possible.

• Rapidly absorbed and excreted
• Half-life = 3.5 hours (dosed 4 times a day; patient compliance drops off)
• Can be difficult on the stomach
• Otitis media (use is declining)
• Previously used to treat UTIs (has good urine solubility)

• Not used often
• Low urine solubility (not good for UTIs); crystallization can be a problem
• Used in combination with other antibacterials to treat nocardial infections and toxoplasmosis (associated with HIV patients, particularly those exposed to cat feces)

• Less soluble in urine and slower excretion than sulfisoxazole, but decent concentrations CAN be reached - Can treat UTIs
• Half-life - 9 hours (dosed twice daily)
• Combined almost exlusively with trimethoprim. They work sequentially in the folate synthesis pathway.
• SYNERGESTIC bactericidal effect

• The most widely used sulfonamide
• Combines two agents which inhibit bacterial synthesis of folinic acid at two sequential steps
• Advantage: Bactericidal-synergestic activity
• Advantage: Slows development of resistance
• Fairly insoluble in IV solutions; a large volume of diluent is needed

•       Increased production of PABA (para-aminobenzoic acid) -

•       Synthesis of an altered dihydropteroate synthetase   and/or dihydrofolate reductase

•       Increased production of dihydropteroate synthetase

•       Reduced drug uptake

•       The optimal synergistic ratio of serum concentrations of TMP-SMX is 1:20

•       Achieved by using a fixed oral or intravenous combination of 1:5 – will ALWAYS be in a 1 to 5 ratio!

• S. aureus (including MSSA and MRSA) >95% activity
• H. influenza – potential cause of meningitis; URI including otitis media
• Stenotrophanomas maltophilia
• L. monocytogenes – Infections in immunocompromised/pregnant patients; outbreaks sometimes from soft cheeses
• P. jiroveci – PCP (pneumocystis pneumonia – pulmonary infections in HIV patients)
• T. gondii (sulfadiazine superior to sulfamethoxazole)

• Enterobacteriaceae
• S. pneumoniae – fairly limited utility against CAP

• S. pyogenes – Strep throat; skin and soft tissue infections
• P. aeruginosa – Many of our sulfas do not cover Pseudomonas, enterococci, or anaerobes
• Enterococci
• Anaerobes

•       Gentiourinary Tract

•       Uncomplicated UTIs (treatment/prevention)

•       GI Tract

•       Prophylaxis for traveler’s diarrhea – not recommended by the CDC to use prophylaxis due to increasing resistance

•       Not useful in treating campylobacter diarrhea

•       Respiratory Infections

•       Acute exacerbations of bronchitis, otitis media, sinusitis

•       Should not be used for streptococcal pharyngitis

•       Treatment & prevention of Pneumocystis pneumonia

•  Alternate Therapy for MRSA, typhoid fever, bacterial prostatitis
• Treatment of Toxoplasma encephalitis

Treatment of community-acquired Methicillin Resistant Staphylococcus aureus  infections (usually skin and soft tissue infections). Oral, inexpensive drug that treats MRSA really well. May be the cause of E. coli resistance to Bactrim.

•       Hypersensitivity Reaction

•       Skin rashes occur in > 3.5% of patients

•       More common in AIDS patients (24-50%)

•       Gastrointestinal

•       Mild nausea/vomiting and diarrhea

•       Hematologic

•       Thrombocytopenia and neutropenia

•       More common in AIDS patients

•       Photosensitivity – Sunburns are common with this medication

•       Nephrolithiasis – Bone marrow degeneration

Contraindications

•       Pregnant Women

•       Should not be used in the third trimester of pregnancy due to risk of kernicterus

•       Avoid use in neonates < 2 months due to immature hepatic enzymes

•       Glucose-6-Phosphate Dehydrogenase Deficiency

•       Increased risk of experiencing hemolytic reactions during therapy

• Folic Acid Deficiency

Patient at increased risk of experiencing hematologic toxicity (i.e. leukopenia, thrombocytopenia)

• TMP-SMX has a significant drug interaction with Warfarin, leading to higher-than-anticipated prothrombin times 

•       A topical sulfa with broad spectrum (including Pseudomonas) used to inhibit bacterial growth on burn wounds

•       Silver ion is an active component (silver is antibacterial)

•       Advantages:  less pain than with mafenide and fewer applications

•       “Local” half-life is longer (it stays in the area longer) – fewer dressing changes

•       Sulfadiazine is absorbed & high concentrations can be achieved - crystaluria can be a problem; you want to maintain adequate renal drug flow

Sulfacetamide

•       Special Use

•       Ophthalmic preparation used to treat superficial infections of the eye

•       Penetrates well into ocular fluids

•       Antimicrobial resistance limits usefulness; occasionally used as a second- or third-line agent for ophthalmic infections

•       You will not see this as an oral or IV preparation

Mafenide

•       Special Uses

•       A broad spectrum topical sulfa

•       Use primarily in burn patients – high risk for infections

•       Avascular tissues commonly infected

•       Poor blood flow due to damaged tissue – higher chance of infection, and difficult to treat (IV and oral abx have a hard time getting to the site of infection when blood flow is hindered)

•       Effective against Pseudomonas aeruginosa; a very common cause of infection in burn patients

•       Diffuses well through devascularized areas, is absorbed, metabolized, and then eliminated by the kidney; systemic toxicity is a potential with this drug due to systemic absorption

Sulfasalazine

•       Special Uses

•       Combination of a sulfa and anti-inflammatory agent

•       Used in the treatment of inflammatory bowel disease

•       Poorly absorbed from the GI tract

•       Metabolized by intestinal bacteria to sulfapyridine (absorbed & renally excreted) & 5-aminosalicylic acid (aspirin)

•       Metabolized to antibacterial and anti-inflammatory compounds

•       Must be given multiple times a day; large tablets

•       Beware of aspirin allergies when using this medication

• mafenide
• silver sulfadiazine