Antibiotics PDF

Antibiotics Assoc. Clinical Professor Samia Hassan  Objectives By the end of this lecture you should be able to: 1) Classify commonly used antibiotics into six major antibiotic classes of; 2) Understand the mechanism of action of each antibiotic class....

Antibiotics Assoc. Clinical Professor Samia Hassan  Objectives By the end of this lecture you should be able to: 1) Classify commonly used antibiotics into six major antibiotic classes of; 2) Understand the mechanism of action of each antibiotic class. 3) Understand clinical use of each class of antibiotic 4) Possible major side effects. There are Three in this Relationship Drug Re si ty s st ic ci Ph D) an et xi (P ar in ce To m ok ac ac od m yn ar am Ph K) ic (P s Infection Host Bacteria Host defence  Antibiotics Actions Bactericidal Kills bacteria, reduces bacterial load Bacteriostatic Inhibit growth and reproduction of bacteria All antibiotics require the immune system to work properly Bactericidal appropriate in poor immunity Bacteriostatic require intact immune system  ß-Lactams ß-Lactams Penicillin Narrow Spectrum Cephalosporin Benzylpenicillin (Penicillin G) Cefalexin Phenoxymethylpenicillin (Pen V) Cefuroxime Flucloxacillin Cefotaxime Broad Spectrum Ceftriaxone Amoxicillin/Co-amoxiclav Ampicillin Carbapenem Piperacillin with Tazobactam Meropenem (Tazocin) Imipenem Doripenem Ertapenem Mechanisms of Action Anti Cell Wall Activity Bactericidal Beta Lactams Against Bacterial Cell Wall Cell wall Osmotic Pressure Cell Membrane Antibiotic against cell wall Osmotic Pressure Cell membrane Rupture Penicillins Penicillins are beta-lactam antibiotics. There are four generations of penicillins. The first three are important in the treatment of ocular infections. The first-generation penicillins are penicillin G and penicillinase-resistant penicillins, of which there are two types, methicillin and nafcillin. Methicillin was used to treat beta-lactamase-producing organisms. Penicillin G is not stabile in gastric acid and is administered parenterally. Methicillin can cause interstitial nephritis and is no longer used in most centers. The penicillins are used specifically to treat ocular infections caused by Streptococcus, Neisseria, Clostridium spp., syphilis, and Actinomyces Treponema pallidum is sensitive to penicillin G, this antibiotic is the drug of choice for treatment of syphilis and syphilitic eye disease. Probenecid can be added to procaine penicillin to decrease excretion of the penicillin by the kidneys, thus causing an increase in penicillin plasma levels. Penicillins are not used for the treatment of minor ocular infections such as blepharitis and conjunctivitis because of the high incidence of allergic reactions when the drug is administered topically. The second-generation penicillins include ampicillin and amoxicillin. These antibiotics have a slightly broader spectrum than those of the first generation. The second- generation penicillins are used to treat ocular infections caused by Haemophilus species and enterococci. The third-generation penicillins are carbenicillin and ticarcillin. Ticarcillin has been combined with clavulanic acid as a suicide inhibitor of beta-lactamase. These antibiotics occupy receptor sites on Gram-negative bacteria making them more active against Gram-negative bacteria. Until recently, carbenicillin was used to treat Pseudomonas infections. Ticarcillin has replaced carbenicillin and may be used in combination with aminoglycosides. The fourth group of penicillins comprises of mezlocillin, piperacillin and azlocillin which are derivatives of ampicillin and are similar to carbenicillin and ticarcillin. These antibiotics are also effective against Gram-negative organisms because they have a greater affinity to cell wall receptor sites in Gram-negative organisms than in Gram- positive organisms. The fourth-generation penicillins have limited role in ophthalmology. New generations of antibiotics are not necessarily better or more effective than earlier generations. Each generation of antibiotics plays a specific role and has specific indication and advantages in the treatment of infections caused by susceptible organisms.  Adverse Effects Penicillin hypersensitivity – 0.4% to 10 % – Mild: rash – Severe: anaphylaxis & death There is cross-reactivity among all Penicillins Penicillins and cephalosporins ~5-15%  Resistance to ß-Lactams ß-Lactamase A combination of 500 mg amoxicillin and 250 mg clavulanic acid (Augmentin®) is effective against beta-lactamase- producing organisms such as Haemophilus and streptococci. The drug is used for the treatment of preseptal cellulitis in young children where Haemophilus is a common cause. Similarly, a combination of ticarcillin and clavulanic acid (Timentin®). Cloxacillin is similar to clavulanic acid (Timentin®) in that it has strong affinity for beta-lactamase and neutralizes its effects.  Important Points Beta lactams need frequent dosing for successful therapeutic outcome – Missing doses will lead to treatment failure Beta lactams are the safest antibiotics in renal and hepatic failure – Adjustments to dose may still be required in severe failure  Cephalosporins Pharmacology Like the penicillins, cephalosporins contain a β-lactam ring that is necessary for antimicrobial activity. It interferes with the terminal step in bacterial cell wall formation. 1st Generation Cephalosporins- cefadroxil & cephalexin - PO; Cefazolin & cephalothin - IM - Gram (+), & gram (-) - Esp. used for skin/skin structure infections - cephalothin used for resp, GI, GU, bone, & joint infections Cefazolin is used in combination with gentamicin or tobramycin to treat bacterial corneal ulcers as part of a broad-spectrum approach. 2nd Generation Cephalosporins - cefaclor - PO, cefoxitin, cefuroxime, cefotetan- IM & IV - Gram (+), slightly boarder gram (-) effect than 1st generation - for harder to treat infections 3rd Generation Cephalosporins - cefotaxime (Claforan), ceftazidime, ceftriaxone (Rocephin) IM or IV, cefixime (Suprax) PO. - More effective against gram (-), less effective against gram (+) Ceftazidime is used as an alternative for topical and intravitreal amikacin, an aminoglycoside, to cover gram-negative organisms including P. aeruginosa, in the treatment of endophthalmitis. Ceftazidime or ceftriaxone combined with nafcillin can be used to treat orbital cellulitis. Ceftriaxone combined with vancomycin can be used to treat moderate to severe preseptal cellulitis Bacitracin; is Bacitracin inhibits bacterial cell wall synthesis by inhibiting the movement. It is active against Neisseria and Actinomyces species, H influenzae, most gram-positive bacilli and cocci, and most but not all strains of MRSA. It is available as an ophthalmic ointment either alone or in various combinations with polymyxin, neomycin, and hydrocortisone. The primary adverse effect is local hypersensitivity, although it is not common. Cell Membrane Function Inhibitors Polymyxin B;. It is used topically or by local injection to treat corneal ulcers. Gram-Negative bacteria including Enterobacter and Klebsiella species and P aeruginosa are susceptible. Systemic use of this medication has been abandoned because of severe nephrotoxicity. Topical hypersensitivity is uncommon. One commercially available topical antibiotic contains polymyxin B sulfate and trimethoprim sulfate.  Glycopeptides Vancomycin Teicoplanin Vancomycin It acts by inhibiting biosynthesis of the bacterial cell wall, It is bactericidal for most gram-positive organisms. Vancomycin is useful in the treatment of staphylococcal infections in patients who are allergic to or have not responded to the penicillins and cephalosporins. It can also be used in combination with aminoglycosides to treat S viridans or Streptococcus bovis endocarditis. Generally, vancomycin is administered intravenously because of poor intestinal absorption. Oral vancomycin is poorly absorbed but is effective in the treatment of pseudomembranous colitis caused by C difficile. Vancomycin resistance hasincreased in isolates of Enterococcus and Staphylococcus,and antibiotic resistance is transmitted between pathogens by a conjugative plasmid. Vancomycin may be used topically or intraocularly to treat infections of the eye, including infectious keratitis and endophthalmitis caused by MRSA or multidrug-resistant streptococci. It has been used within the irrigating fluid of balanced salt solution during intraocular surgery. Vancomycin is a preferred substitute for a cephalosporin used in combination with an aminoglycoside in the empirical treatment of endophthalmitis. Topical and intraocular vancomycin has not been associated with ototoxicity or nephrotoxicity. In addition to the ototoxicity and nephrotoxicity associated with systemic therapy, possible complications include chills, rash, fever, and anaphylaxis. Furthermore, rapid intravenous infusion may cause “red man syndrome” due to flushing. Drugs Affecting Protein Synthesis Antibacterial drugs that affect bacterial protein synthesis Chloramphenicol, Aminoglycosides, Tetracyclines Macrolides,  Chloramphenicol Pharmacology Chloramphenicol inhibits protein synthesis by binding to the 50S. Clinical use This remains the most commonly used topical antibiotic in the UK and Australasia for the prophylaxis of ocular bacterial infections and is a very useful first-line treatment for bacterial conjunctivitis. Chloramphenicol is active against most gram-positive and gram-negative bacteria, Rickettsia, Chlamydia, spirochetes, and Mycoplasma; however P. aeruginosa is resistant to this drug. Chloramphenicol is widely available as 0.5% drops and a one percent ointment, in addition to a reasonable spectrum of antibacterial activity it has low topical toxicity, and since it has extremely limited use in the community - other than for ophthalmic conditions - there is very limited bacterial resistance. However, it is not used routinely for more severe infections such as bacterial keratitis, and there is a theoretical risk of aplastic anaemia. Side Effects Chloramphenicol causes; The first is a dose-related toxic effect causinga bone marrow depression. A second, more serious, type of bone marrow depression consists of aplastic anemia. Aplastic anemia occurs most commonly weeks to months after completion of therapy.  Aminoglycosides Inhibit bacterial protein synthesis by irreversibly binding to 30S ribosomal unit Naturally occurring: Streptomycin Neomycin Kanamycin Tobramycin Gentamicin Semisynthetic derivatives: Amikacin (from Kanamycin) Netilmicin (from Sisomicin)  30S Ribosomal Unit Blockage by Aminoglycosides Aminoglycosides are rapidly bacteriacidal and inhibit protein synthesis. Pharmacokinetics; Aminoglycosid are water-soluble and do not readily cross cell membranes. Aminoglycosides are distributed well into extracellular fluid except for vitreous humor. Intravitreous injection is required to treat endophthalmitis. Clinical use; Aminoglycosides’ broad spectrum of activity includes: P. aeruginosa, Proteus, Klebsiella, E. coli, Enterobacter, and Serratia and Staphylococcus aureus There are a number of aminoglycosides in use including framycetin, neomycin, tobramycin, gentamicin, amikacin and streptomycin. However, the most popular of these are neomycin, tobramycin which has a wide spectrum of activity against bacteria, and gentamicin which is usually reserved for severe corneal infections. Tobramycin is a superior antibacterial than gentamicin and is active against a spectrum of Gram positive and Gram negative bacteria, including pseudomonas. It is active against most ocular staphylococci and is the first-line antibiotic for ocular bacterial for topical ophthalmic use. Due to tobramycin's broad spectrum of activity, it has proven useful in controlling both superficial and deep infections of the eye and ocular adnexa (i.e., blepharitis, conjunctivitis, keratitis, and endophthalmitis). However, since tobramycin has been associated with neuromuscular blockade, as well as possessing ototoxic and nephrotoxic effects, care must be taken to minimize toxicity by monitoring patients undergoing systemic tobramycin therapy. Amikacin; was the first semisynthetic aminoglycoside to be marketed it has become the preferred drug for treatment of gram- negative bacillary infections in which resistance to both gentamicin and tobramycin is encountered. At the clinical level, however, evidence is lacking that amikacin is more efficacious than gentamicin or tobramycin for infections caused by susceptible organisms. Because amikacin is less toxic when injected intravitreally, it has become a primary antibiotic, along with vancomycin, for treatment of bacterial endophthalmitis. Gentamicin has been used in the treatment of Endophthalmitis Anterior segment infection Postoperative prophylaxis because of its activity against Gram-negative organisms.  It is cleared from the eye by the anterior chamber and has a half-life of 33 hours. Although aminoglycosides are well known to be associated with oto- and nephrotoxicity with systemic use, it has recently been recognized that there is ocular toxicity with local administration as well.  Loss of visual function has been reported after administration of gentamicin  Streptomycin has limited uses because of resistance and toxicity. It is used, to treat tuberculosis of the eye. Tuberculous of cornea, conjunctive, iris and retainal veins is secondary to general infection this not exclude local therapy as an agent of some value. Neomycin is limited to topical use in small amounts. Neomycin is available for eye, ear, oral, and rectal use and as a bladder irrigant. Oral neomycin is used topically against intestinal to prepare the bowel before surgery and to treat hepatic coma. it causes eight cranial nerve damage, especially if there is renal impairment. Kanamycin may still play a role in the treatment of certain cases of multidrug-resistant tuberculosis in combination with other antibiotics.  Adverse Effects Nephrotoxicity – Direct proximal tubular damage - reversible if caught early – Risk factors: High troughs, prolonged duration of therapy, underlying renal dysfunction, concomitant nephrotoxins Ototoxicity – 8th cranial nerve damage – irreversible vestibular and auditory toxicity Vestibular: dizziness, vertigo, ataxia Auditory: tinnitus, decreased hearing – Risk factors: as for nephrotoxicity Neuromuscular paralysis – Can occur after rapid IV infusion especially with; Myasthenia gravis Concurrent use of succinylcholine during anaesthesia Several cases of retinal toxicity have been reported after aminoglycoside use for the treatment or prophylaxis of endophthalmitis. Loss of visual function has been reported after adminis Retinal damage in the form of macular infarction has occurred after intravitreal administration of gentamicin. tration of gentamicin, amikacin, and tobramycin. Glaucoma, pigmentary degeneration, optic atrophy, and severe visual loss. Punctate epithelial erosions, delayed reepithelialization, and corneal ulceration. Aminoglycoside-induced macular infarction. This patient was given a subconjunctival injection of gentamicin following uncomplicated cataract surgery.  Prevention of Toxicity a) Levels need to be monitored to prevent toxicity due to high serum levels b) To be avoided where risk factors for renal damage exist 1) Dehydration 2) Renal toxic drugs  Important Points Aminoglycosides should be given as a large single dose for a successful therapeutic outcome – Multiple small doses will lead to treatment failure and likely to lead to renal toxicity Aminoglycosides are toxic drugs and require monitoring – Avoid use in renal failure but safe in liver failure – Avoid concomitant use with other renal toxic drugs – Check renal clearance, frequency according to renal function  Macrolides Azithromycin, Erythromycin, Clarithromycin, Roxithromycin, Relithromycin and Fidaxomicin Macrolides Lactone Ring 14 14 Erythromycin Telithromycin 15 14 Clarithromycin Azithromycin  Mechanism of Action Bacteriostatic- usually, they may be bactericidal at high doses. Inhibit bacterial RNA-dependent protein synthesis – Antimicrobial binds to the 50S ribosomal subunit of susceptible microorganisms and interferes with microbial protein synthesis.  Spectrum of Activity Gram-Positive Aerobes: – Activity: Clarithromycin>Erythromycin>Azithromycin S. pneumoniae Beta haemolytic streptococci and viridans streptococci Gram-Negative Aerobes: – Activity: Azithromycin>Clarithromycin>Erythromycin H. influenzae, M. catarrhalis, Neisseria sp. NO activity against Enterobacteriaceae Anaerobes: upper airway anaerobes Atypical Bacteria Azithromycin;. It has been effective against chlamydial infections. A single, 1-g dose is sufficient to eradicate it. Azithromycin is effective in the treatment of trachoma. A 1-week course or repeated 3-day courses of azithromycin are required in chronic active cases of trachoma Gram-positive bacteria. Haemophilus influenzae Azithromycin has a long elimination life reaching 68 h. Azithromycin is recently adapted for topical use in ophthalmology; purulent bacterial conjunctivitis, Meibomian gland dysfunction, blepharitis, and papulopustula rosacea. Azithromycin is used for the treatment of chlamydial conjunctivitis, trachoma, keratitis due to Mycobacterium chelonae, and chronic blepharitis It appears that dryness may increase the tissue absorption of the cornea. Common side effects of Azithromycin Ophthalmic include: Eye irritation, Dry or itchy eyes, Blurred vision, Stuffy nose, and Changes in the sense of taste Difficulty breathing, Swelling of the face, lips, tongue, or throat, Fever, Sore throat, Burning eyes, Skin pain. Red or purple skin rash with blistering and peeling, Severe burning, stinging, other irritation after using the eye drops, Feeling like something is in the eye, Changes to the surface of the eye, Eye pain or swelling, Eyelid irritation, and any signs of a new infection Erythromycin : Exerts effect only against multiplying organisms; penetrates cell wall of gram-positive bacteria more readily than that of gram- negative bacteria. Bacterial conjunctivitis –Blepharitis – Neonatal conjunctivitis – A type of conjunctivitis in newborns that develops if chlamydia or gonorrhea bacteria Approximately 30 % of staphylococci isolated from ocular infection are resistant to erythromycin. Erythromycin cannot be considered the drug of choice for the treatment of infections caused by these organisms. Side effects; Burning, stinging or itching of the eyes or eyelids Changes in vision Redness, swelling or pain in or around the eyes. Clarithromycin and Telithromycin widely penetrates and adequately concentrates in the aqueous humor, vitreous humor, and iris tissue after oral administration and therefore is effective in the management of many infectious ocular conditions. It effective against Haemophilus influenzae and has greater activity against intracellular pathogens such as Chlamydia, Legionella, Moraxella and Helicobacter pylori. treatment of Mycobacterium avium complex. Telithromycin is the structural modification within ketolides neutralizes the most common resistance mechanisms Lincosamid; Clindamycin, Lincomycin - PO, IM, IV - Inhibit bacterial protein synthesis it is similar to erythromycin - ‘Static’ & ‘cidal’ actions depending on drug dosage - effective against most gram (+), no gram (-) Clindamycin is well absorbed from the gut and distributes to most body tissues including bone, but only small quantities reach the eye. - Clindamycin more effective than lincomycin Oxazolidinone: (Linezolid) Linezolid inhibits protein synthesis and appears to work by disrupting the translation of messenger RNA into proteins in the ribosomes. Linezolid binds to 50S subunit of the ribosome. that linezolid is most active against Gram-positive bacteria including streptococci, vancomycin-resistant-enterococci, and methicillin-resist, resistant-Staphylococcus aureus (MRSA). The main indications of linezolid are infections of the skin and soft tissues and pneumonia. microbiologically significant levels of linezolid can rapidly be achieved in the aqueous humor of the noninflamed human eye after intravenous administration of 600 mg. Two hours after administration of the antibiotic, the levels obtained were higher than the MIC at which 90% of Staphylococcus epidermidis strains are inhibited Fluoroquinolones Quinolone pharmacore Fluoroquinolones Fluoroquinolones are synthetic fluorinated derivatives of nalidixic acid. These drugs are highly effective broad-spectrum antimicrobials with potent activity against common gram- positive and gram-negative ocular pathogens. Their mechanism of action targets bacterial DNA supercoiling. Fluoroquinolone resistance has been reported in Mycobacterium chelonae, S aureus, coagulase-negative Staphylococcus species, Pseudomonas aeruginosa, Clostridium difficile, Salmonella enterica, E coli, and Helicobacter pylori. In vitro studies have demonstrated that the fluoroquinolones, especially ciprofloxacin and temafloxacin, inhibit 90% of common corneal bacterial pathogens and have a lower minimum inhibitory concentration than that of the aminoglycosides gentamicin and tobramycin and the cephalosporin cefazolin. They are also less toxic to the corneal epithelium than are the aminoglycosides. Methicillin-susceptible strains of S aureus are generally susceptible to fluoroquinolones, but methicillin-resistant strains of staphylococci are often resistant to them. Seven currently available topical fluoroquinolones are ofloxacin ophthalmic solution, 0.3%; ciprofloxacin, 0.3%; levofloxacin, 0.5%; gatifloxacin, 0.3% and 0.5%; moxifloxacin, 0.5%; norfloxacin, 0.3%; and besifloxacin, 0.6%. They are used to treat corneal ulcers caused by susceptible strains of S aureus, S epidermidis, Streptococcus pneumoniae, P aeruginosa, Serratia marcescens (efficacy studied in fewer than 10 infections), and Propionibacterium acnes. They are also indicated for bacterial conjunctivitis due to susceptible strains of S aureus, S epidermidis, S pneumoniae, Enterobacter cloacae, H influenzae, P mirabilis, and P aeruginosa. These fluoroquinolones have a high rate of penetration into ocular tissue. Their sustained tear concentration levels exceed the minimum inhibitory concentrations of key ocular pathogens for 12 hours or more after 1 dose. They also deliver excellent susceptibility kill rates; 1 in vitro study confirmed eradication of 87%–100% of indicated pathogenic bacteria, including P aeruginosa. Ofloxacin has a high intrinsic solubility that enables formulation at a near-neutral pH of 6.4. Ciprofloxacin is formulated at a pH of 4.5, gatifloxacin at a pH of 6.0, and moxifloxacin at a pH of 6.8. Adverse reaction with fluoroquinolones is Transient ocular burning or discomfort. Other reported reactions are stinging, redness, itching, chemical conjunctivitis/keratitis, periocular/facial edema, foreign-body sensation, photophobia, blurred vision, tearing, dry eye, and eye pain. Though rare, dizziness has also been reported. Both norfloxacin and ciprofloxacin have caused white, crystalline corneal deposits of medication, which have resolved after discontinuation of the drug. Ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, gatifloxacin, and moxifloxacin are available as topical ophthalmic solutions, and ciprofloxacin is available as an ophthalmic ointment. These drugs are broad spectrum and effective against both gram-positive and gram-negative bacteria. However, the clinical utility and effectiveness of the older fluoroquinolones (ciprofloxacin, norfloxacin, and ofloxacin) have been eroded due to growing rate of resistance, particularly among gram-positive bacteria. Moxifloxacin and gatifloxacin have enhanced activity against gram-positive bacteria while maintaining potency against gram-negative bacteria. These fourth-generation quinolones are active not only against fluoroquinolone-resistant staphylococci and streptococci, but also against penicillin- and macrolide- resistant isolates as well. The suggested regimen for ciprofloxacin therapy is one to two drops applied to the affected eye every 15 minutes for the first 6 hours and then every 30 minutes for the rest of the day. The dosage on day 2 is one to two drops every hour.  Tetracyclines Tetracycline; Short acting Oxytetracycline; Intermediate acting Doxycycline; Long acting Doxycycline is the preferred tetracycline because it is better absorbed and distributed than the others  Mechanism of Action Tetracyclines inhibit bacterial protein synthesis by binding to the 30S subunit of the ribosome, thus blocking the attachment of aminoacyl-tRNA to the receptor site on the messenger RNA–ribosome complex. Bacteriostatic for a wide variety of infections caused by less common pathogens. These include brucellosis; rickettsial infections such as Rocky Mountain spotted fever, typhus, and Q fever; Mycoplasma pneumonia; cholera; plague; Ureaplasma urethritis; Chlamydia infections; and Lyme disease. Oral doxycycline, 100 mg orally twice a day for 7 days, is a recommended treatment for chlamydial sexually transmitted disease. In adults with chlamydial ocular infections such as inclusion conjunctivitis or trachoma, treatment with oral doxycycline or tetracycline. In community-based programs to control trachoma, topical tetracycline ointment administered twice daily on an intermittent schedule (5 consecutive days each month for 6 months) can be useful. However, incomplete cure and subsequent disease transmission can result. In contrast, oral treatment with tetracycline or doxycycline cures trachoma. Oral tetracycline or doxycycline can be an effective therapy for noninfectious conditions involving the eye such as acne rosacea and meibomianitis. When patients with acne rosacea or meibomianitis receive oral tetracycline, two changes occur: amelioration of the symptoms and reduction of free fatty acids in the surface sebum.  Adverse Effects Oesophageal ulceration Photosensitivity reaction Incorporate into foetal and children bone and teeth, Intracranial hypertension Avoid in pregnancy and children  Glycylcyclines (e.g., tigecycline It is semisynthetic derivatives of tetracycline and they binds to the 30S subunit of bacterial ribosomes to impair protein synthesis. They were designed to avoid the efflux-mediated resistance mechanisms that have plagued the tetracycline class. Glycylcyclines are active against methicillin resistant Staphylococcus (MRSA) and methicillin- resistant Staphylococcus epidermidis (MRSE), penicillin- resistant Streptococcus pneumoniae (PRSP), and vancomycin- resistant enterococci bacteria (VRE). Tigecycline is given intravenously and is well distributed in tissues. It has a very long half-life (about 27–42 hours). The most side effects acute pancreatitis, elevations in liver enzymes Use of Pharmacokinetics in Treatment Beta lactams Aminoglycosides Good/variable (Dependant on individual antibiotic) Good Soft tissue Circulating organisms Bone and joints Lungs Poor CSF Soft tissue Poor Bone and joints Abscesses Abscesses Lungs CSF Examples of good Tissue Penetrators Tetracyclines Macrolides Quinolones Clindamycin Sulfonamides They are competitive antagonists of dihydropteroate synthase for the bacterial synthesis of folic acid. Sulfonamides are bacteriostatic only and are more effective when administered with trimethoprim or pyrimethamine, each of which is a potent inhibitor of bacterial dihydrofolate reductase Sulfacetamide ophthalmic solution (10%–30%) and ointment (10%) penetrate the cornea well. Susceptible organisms include; S pneumoniae, Corynebacterium diphtheriae, H influenzae, Actinomyces species, and Chlamydia trachomatis. adverse effects from topical administration; Local irritation, itching, periorbital edema, and transient stinging. As for all sulfonamide preparations, severe sensitivity reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported. The incidence of adverse reactions to all sulfonamides is approximately 5%.