Antimicrobial agents (AMAs) : Adverse Effects, Drugs

SULFONAMIDES

Sulfonamides were the first antimicrobial agents (AMAs) effective against pyogenic bacterial infections.

Sulfonamido-chrysoidine (Prontosil Red) was one of the dyes used to treat experimental streptococcal infection in mice and found it to be highly effective.

Subsequently, an infant was cured of staphylo- coccal septicaemia by protonsil.

1. Short acting (4-8 hr): Sulfadiazine
2. Intermediate acting (8 12 hr):

Sulfamethoxazole

3. Long acting (7 days ) Sulfadoxine, Sulfamethopyrazine
4. Special purpose sulfonamides:

Sulfacetamide sodium, Mafenide, Silver sulfadiazine, Sulfasalazine

Antibacterial Spectrum

Sulfonamides are primarily bacteriostatic against many gram-positive and gram-negative bacteria.

Therapeutics

Sulfonamides have a broad spectrum of antimicrobial activity against many microorganisms including bacteria and some protozoa, such as Toxoplasma and Plasmodia.

Currently, they are most commonly to treat acute urinary tract infections. They are also often used in combinations with other agents, such as trimethoprim and pyrimethamine for the treatment of parasitic diseases.

Contraindications

The sulfonamindes are contraindicated in those known to be hypersensitive to them, in infants less than 2 months of age, during pregnancy, and in nursing mothers.

Adverse Effects

Most troubling side effect is hypersensitivity reactions and effects on the hematopoietic system. Hypersensitivity reactions to sulfonamides are quite variable and include a variety of rashes, erythema nodosum, erythema multiforme of the Stevens-Johnson type, exfoliative dermatitis, and photosensitivity.

Hematopoietic effects are most common with some of the older, long-acting sulfonamides and include acute hemolytic anemia, agranulocytosis, and aplastic anemia.

Drugs used

Sulfadiazine is an antibiotic. Used together with pyrimethamine, it is the treatment of choice for toxoplasmosis. It is a second-line treatment for otitis media, prevention of rheumatic fever, chancroid, chlamydia, and infections by Haemophilus influenzae. It is taken by mouth.

Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infectionssuch as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as Listeria monocytogenes and E. coli.

Sulfadoxine (also spelled sulphadoxine) is an ultra-long-lasting sulfonamide (Antimicrobial agents) used in combination with pyrimethamine to treat malaria.

Sulfacetamide sodium This medication is used to treat bacterial eye infections (such as conjunctivitis). It belongs to a class of drugs known as sulfa antibiotics.

Mafenide is an antimicrobial agent used to treat severe burns. It acts by reducing the bacterial population present in the burn tissue and promotes healing of deep burns.

Silver sulfadiazine is used to prevent and treat infections of second- and third-degree burns. It kills a wide variety of bacteria.

Sulfasalazine (Azulfidine) is considered a disease-modifying anti-rheumatic drug (DMARD).

It can decrease the pain and swelling of arthritis, prevent joint damage, and reduce the risk of long term disability.

QUINOLONES

These are synthetic antimicrobial agents having a quinolone structure that are active primarily against gram-negative bacteria.

The first member Nalidixic acid introduced usefulness limited to urinary and GI tract infections have high frequency of bacterial resistance.

The most popular quinolones are fluoroquinolones, which include ciprofloxacin (Cipro), lomefloxacin (Maxaquin), norfloxacin (Noroxin), ofloxacin (Floxin), moxifloxacin (Avelox) and levofloxacin (Levaquin).

COTRIMOXAZOLE

Co-trimoxazole is a combination antibiotic sulfamethoxazole and trimethoprim.

It can be taken by people who are allergic to penicillin, but it is not suitable for people who are allergic to sulfonamides.

The most common side-effects are feeling sick, diarrhoea and headache. Also a skin rash or any allergic-type reaction can develop.

It is prescribed for infections which can occur in people who have a problem with their immune systems. It works by killing the germs (bacteria) responsible for causing the infection.

Though cotrimoxazole is still used, its popularity in the treatment of systemic infections has declined. Common indications are:

1. Urinary tract infections= Most acute uncomplicated infections respond rapidly. Single dose therapy with 4 tablets of cotrimoxazole has been used successfully for acute cystitis.

Courses of 3-10 days have been advised for lower and upper urinary tract infections, according to associated features. Cotrimoxazole is specially valuable for chronic or recurrent cases or in prostatitis, because trimethoprim is concentrated in prostate.

2. Respiratory tract infections= Both upper and lower respiratory tract infections, including chronic bronchitis and facio-maxillary infec tion, otitis media caused by gram positive cocci and H. influenzae respond well.
3. Bacterial diarrhoea and dysentery= Cotri moxazole may be used for severe and invasive infections by E. coli, Shigella, non typhoid Salmonella, and Y. enterocolitica (see p. 682).

Though response rate is lower than previously, and fluoroquinolones are more commonly used, it is still a valuable alternative for empirical therapy of infective diarrhoea.

4. Pneumocystis jiroveci causes severe pneumonia in neutropenic and AIDS patients.

Cotrimoxazole has prophylactic as well as therapeutic value, but high doses are needed. One DS tablet 4-6 times/day for 2-3 weeks may be curative, but adverse effects necessitate discontinuation in upto 20% cases. One DS tab. daily has been used for prophylaxis and this is better tolerated.

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