Information on anti bacterial drugs

Antimicrobial agents have been one of the most important, and successful, groups of therapeutic agent introduced. Initially these agents were discovered and developed empirically (for example, sulphonamides and penicillin). The search for new antibiotics then involved screening of biological materials such as sewage and soil specimens to look for antimicrobial substances produced by organisms. Cephalosporins were discovered as agents produced from a sewage sample from Sardinia. Such screening processes are now largely regarded as dated and most screening takes place using a highly mechanised combinatorial approach in which vast numbers of organic molecules are tested for antimicrobial activity. Promising compounds are then identified and chemically modified to produce higher antimicrobial activity and the desired antimicrobial spectrum of activity. Agents discovered and refined in this way are already in phase III testing and will reach clinical use in the near future.

THE β-LACTAM ANTIBIOTICS

These are the penicillins and cephalosporins whose basic structure includes a four-membered 3-lactam ring . Resistance is commonly due to bacterial enzymes called β-lactamases (penicillinases and cephalosporinases) which can cleave the ring and inactivate the antibiotic. The plasmids which code for these enzymes are transmissible between bacteria. Resistance may also be due to other mechanisms such as inability of the antibiotics to penetrate the bacterial cell wall. Pemcillin-resistant pneumococci and meningococci MRSA), which are and methicillin-resistant staphylococci (also resistant to cloxacillin, are increasing problems in many countries.

The penicillins

All penicillins are bactericidal, killing bacteria by interfering with their cell wall synthetic processes. The range of their activity is wide. as both Gram-positive and certain Gram

The penicillins
	β-lactamase stable	Route of administration	Average adult dose (mg given 6-hourly)	Indications
Benzylpenicillin	-	Parenteral	600-2400	Streptococcal and meningococcal infections anthrax, diphtheria, gas gangrene, syphilis, yaws, gonorrhoea, actinomycosis
Procaine penicillin	-	Parenteral	300 (daily)	As for benzylpenicillin
Phenoxymethylpenicillin	-	Oral	500	Mild streptococcal infections
Cloxacillin/flucloxacillin	+	Parenteral/oral	500-2000	Staphylococcal infections
Ampicillin/amoxycillin	-	Parenteral/oral	250-1000	Infections caused by aerobic Gram-negative bacilli, streptococci, salmonellae and shigellae
Amoxycillin plus clavulanic acid (Augmentin)	+	Parenteral/oral	250-1000 (amoxycillin dose)	As for amoxycillin plus staphylococci and bacteroides
Ampicillin plus sulbactam (sultamicillin)	+	Oral	375 (12-hourly)	Infections caused by susceptible organisms and surgical prophylaxis where β-lactamase inhibition is required
Carbenicillin	-	Parenteral	1000-5000	Pseudomonas infections
Ticarcillin	-	Parenteral	1000-5000	Pseudomonas infections
Ticarcillin plus clavulanic acid (Timentin)	+	Parenteral	3200 (6-8-hourly)	Pseudomonas and Proteus infections
Azlocillin	-	Parenteral	1000-5000	Pseudomonas infections
Mezlocillin		Parenteral	1000-5000
Piperacillin	-	Parenteral	1000-5000	Infections caused by aerobic Gram-negative bacilli and surgical prophylaxis (bowel and pelvic surgery)
Temocillin	+	Parenteral	1000-2000 (12-hourly)	Infections caused by aerobic Gram-negative bacilli Infections caused by Gram-negative bacilli

negative organisms are sensitive to individual penicillin. Their most important adverse effect hypersensitivity see the information hoxy This may take the form of urticaria and pyrexia or an acute anaphylac reaction which may occasionally prove fatal.

The penicillin ADVERSE EFFECTS OF THE PENICILLINS
Hypersensitivity Skin rash (urticaria or maculo papular) Anaphylaxis Drug fever Interstitial nephritis	Dose related Encephalopathy Neutropenia (reversible) Haemolysis

Although penicillin is otherwise a safe antibiotic, it accumulation in patients with renal failure may lead to encephalopathy. In these patients dosage must be modified and guided by blood levels. In severe infections penicillin should be given intravenously, it should never be given intrathecally due to risk of seizure.

Benzylpenicillin

This is rapidly absorbed following intramuscular injection and is excreted by the kidneys within a few hours Probenecid, 2 g daily by mouth, will raise the blood level of penicillin by delaying its excretion by the kidney and thus allow smaller doses or less frequent administration. Penicillin is also used prophylactically to prevent endocarditis, tetanus and gas gangrene.

Phenoxymethylpenicillin

This is incompletely absorbed from the stomach and is only used for less serious infections such as tonsillitis.

Cloxacillin and flucloxacillin

These are semi-synthetic penicillins which are stable to staphylococcal β-lactamases. For oral therapy, flucloxacillin is superior to cloxacillin as it is almost twice as well absorbed from the gut.

Temocillin

This is active against penicillinase-producing Gram-negative bacilli.

Ampicillin

This is a semi-synthetic penicillin which has a bactericidal action against both Gram-positive and certain Gram-negative organisms. It is susceptible to degradation by β -lactamases and not well absorbed with food. Maculo-papular rashes occur in approximately 5% of all patients given ampicillin and in over 90% of patients given it for infectious mononucleosis: this antibiotic should not therefore be prescribed for sore throats which may be due to infectious mononucleosis. There are a number of ampicillin esters including bacampicillin and pivampicillin. These are better absorbed and produce higher blood levels of ampicillin.

Amoxycillin

This is an analogue of ampicillin which has a similar antibacterial spectrum but is more reliably absorbed from the gastrointestinal tract. Clavulanic acid is a β-lactam agent with only weak antibacterial activity. It is, however, a potent inhibitor of many β-lactamases and can protect β-lactamase-susceptible antibiotics, such as amoxycillin, from inactivation by these enzymes. A combination of amoxycillin plus sodium clavulanate (ratio 1:2 oral and 1:5 i.v.) is available (Augmentin). There is also a combination of ampicillin and another β-lactamase inhibitor called sulbactam (Unasyn).

Ticarcillin

Carbenicillin was initially the only penicillin with activity against Pseudomonas aeruginosa. This organism, however, is only moderately sensitive to carbenicillin, which has been replaced by its more active analogue ticarcillin. There is a preparation containing ticarcillin plus clavulanic acid (Timentin).

Mezlocillin, azlocillin and piperacillin

These acylureidopenicillins have a wider range of activity than ampicillin and are also more effective against many Gram-negative bacilli. They are used in combination with other antibiotics for the treatment of undiagnosed infections in immunocompromised patients. Azlocillin is more active than ticarcillin against Ps. aeruginosa, and is usually used in combination with an aminoglycoside for Pseudomonas infections. Piperacillin also has anti-anaerobic activity.

The cephalosporins

The cephalosporins have a wide range of activity against many important Gram-positive and Gram-negative bacteria and are therefore of value for the treatment of serious infections and for the initial empirical therapy of undiagnosed infections. The information box lists the cephalosporins available in 1998. They have been developed over the past 30 years and the historical classification by 'generations', although helpful, is not ideal. A more systematic approach based on groupings according to antimicrobial activity and 3-lactamase production has been suggested and categorises cephalosporins into seven groups (see O'Grady et al, Further information). The firstgeneration agents developed in the 1960s have generally been replaced by the newer compounds. The secondgeneration drugs are more stable to 3-lactamases. The third-generation agents are more active than the second against Gram-negative bacilli; however, they are less active

CEPHALOSPORINS
Injectable
First generation Cephradine (also oral) Cephazolin Second generation Cefamandole Cefuroxime (also oral)	Third generation Cefotaxime Ceftazidime Ceftizoxime Cefodizime Cefpirome Cefsulodin (Pseudomonas infections only) Ceftriaxone (long serum half-life) Fourth generation Cefepime Cefpirome
Oral
First generation Cephalexin Cephradine Cefadroxil Second generation Cefaclor Cefixime Ceftibuten Cefuroxime axetil	Third generation Cefpodoxime proxetil

against Gram-positive bacteria, especially Staph, aureus. The third-generation agents are very expensive.

Cefoxitin, a broad-spectrum cephamycin antibiotic, has activity against Bacteroides fragilis, an anaerobic bacillus which is a common cause of intra-abdominal sepsis, and is used for such infections.

The orally active cephalosporins are principally used for the treatment of lower respiratory tract, ear and urinary tract infections. They all have a similar spectrum but the newer agents are more resistant to β-lactamases.

The dose of the cephalosporins ranges from 250–2000 mg 6-8-hourly, depending on the weight of the patient, renal function and severity of infection. Ceftazidime is the most active against Gram-negative bacilli and is specifically useful in Pseudomonas infection. It is used for the treatment of septicaemia and infections in the immunocompromised. Ceftriaxone has a much longer serum half-life (10 hours) than the other cephalosporins (1 hour) and need only be given once daily. Agents such as cefotaxime and ceftriaxone are now used extensively for the treatment of meningitis.

Adverse reactions are similar to those of the penicillins. A small number (around 10%) of penicillin-sensitive patients may also be allergic to the cephalosporins, which should be avo:ded if there is a history of significant hypersensitivity to the penicillins.

Other β-lactam agents

Imipenem

This is a β-lactam antibiotic with a very broad spectrum which includes aerobic and anaerobic Gram-positive and Gram-negative organisms. It is partially inactivated by a renal enzyme and is therefore given along with an inhibitor of this enzyme called cilastatin. Side-effects are similar to other β-lactam antibiotics. Aztreonam This is a monocyclic ß-lactam antibiotic, the efficacy of which is limited to Gram-negative aerobic bacteria including Ps. aeruginosa and Haemophilus influenzae. Side-effects are similar to those of other β-lactam antibiotics.

THE MACROLIDE ANTIBIOTICS

These are erythromycin, clarithromycin, azithromycin and spiramycin.

Erythromycin

This has a similar although not identical spectrum to penicillin and is commonly used to treat infections caused by Gram-positive organisms in penicillin-allergic patients in combination with fusidic acid. It is also effective in whooping cough, Campylobacter enteritis and legionnaires' disease, provided it is given early enough in the course of these illnesses. Many physicians now use erythromycin as first-line treatment for community-acquired pneumonia in view of its wider spectrum of activity than penicillin.It has activity against mycoplasmas and chlamydiae and is an effective antibiotic for the treatment of many acute respiratory infections. Erythromycin is prescribed in a dosage of 250-500 mg by mouth 6-hourly. There is a preparation for intravenous injection which is highly thrombophlebitic. Diarrhoea, vomiting and abdominal pain are the principal side-effects. Cholestatic jaundice may rarely develop if the course of treatment exceeds 10 days.

Clarithromycin

This has slightly greater activity than erythromycin, and achieves higher concentrations in tissues. The dose is 200-500 mg 12-hourly. sed.

Azithromycin

This has more activity than erythromycin against certain Gram-negative organisms, including H. influenzae, but is less active against Gram-positive bacteria. As with clarithromycin, tissue levels are high but plasma levels are low. The serum half-life is long, allowing once-daily administration (500 mg). Due to their greater activity against H. influenzae and also against the organisms causing atypical pneumonia (mycoplasma, chlamydia and Legionella), clarithromycin and azithromycin may replace erythromycin for the treatment of lower respiratory tract infections.

Spiramycin

This is a macrolide used as second-line treatment for toxoplasmosis.

THE TETRACYCLINE ANTIBIOTICS

Tetracycline, oxytetracycline, chlortetracycline and minocycline are closely related bacteriostatic agents which, for practical purposes, have an identical range of activity, The adult dose is 250-500 mg 6-hourly before meals because the absorption of most tetracyclines is reduced by chelation with calcium (e.g. in milk). Doxycycline is an exception and also has the advantage that it is given only once daily, 200 mg on the first day and 100 mg thereafter.

The tetracyclines inhibit the growth of a wide range of Gram-positive and Gram-negative bacteria although in the context of treating lower respiratory tract infections their value is limited by the emergence of tetracycline-resistant pneumococci and H. influenzae. The tetracyclines are also active against rickettsiae (typhus fevers), Coxiella burnetii (Q fever), Mycoplasma pneumoniae and chlamydiae (lymphogranuloma venereum, psittacosis and non-gonococcal urethritis) and are effective in brucellosis. They are also employed systemically in acne vulgaris and rosacea where their beneficial effect is not due solely to their antibacterial action. Chlortetracycline is used for the local treatment of skin infections as it does not cause cutaneous sensitisation.

The tetracyclines are generally safe antibiotics, with few side-effects. The most common is diarrhoea, which usually stops when the antibiotic is discontinued. Tetracyclines chelate with calcium and are deposited in developing bone and teeth, causing a brown discoloration. They should not therefore be given to children or pregnant women. With the exception of doxycycline and minocycline, the tetracyclines can exacerbate renal failure and should not be given to patients with impaired renal function.

THE AMINOGLYCOSIDE ANTIBIOTICS

Streptomycin, gentamicin, tobramycin, netilmicin, amikacin and neomycin have similar chemical structures and adverse effects. They are not absorbed and for systemic treatment must be given by injection (except neomycin).

Streptomycin

This has the important property that it is bactericidal against the tubercle bacillus . It is given with two other antituberculous drugs and this triple therapy prevents the emergence of resistant strains. For long-term therapy the daily dose of streptomycin should not exceed 1 g. It is also useful in the treatment of brucellosis.

Gentamicin

This is active against most Gram-negative bacilli, including Ps. aeruginosa. It is also active against penicillin-resistant staphylococci but inactive against anaerobes and streptococci with the exception of Enterococcus faecalis; in serious infections caused by this organism gentamicin is combined with ampicillin. The dose of gentamicin depends on renal function and the age and weight of the patient; 5 mg/kg body weight per 24 hours in divided doses

The aminoglycosides: dosages
			Maximum plasma levels
Aminoglycoside	Max. daily dose (mg/kg/24 hrs)	Peak level	Pre-dose level
Gentamicin	5	10 mg/l	2 mg/l
Tobramycin	5	10 mg/l	2 mg/l
Netilmicin	6	12 mg/l	2 mg/l
Amikacin	10	30 mg/l	10 mg/l
Notes 1. Plasma levels should be monitored in all patients if possible and MUST be measured in the elderly, in infants, and if high doses are given or IF RENAL FUNCTION IS IMPAIRED. 2. Gentamicin, tobramycin and netilmicin are usually given 8- or 12-hourly if renal function is normal. Single daily dosage is also effective. 3. 60-80 mg 12-hourly of gentamicin is recommended for streptococcal endocarditis.

(usually given 8-hourly) is indicated for most infections. Recent evidence shows that single daily dosing is effective. A loading dose of gentamicin is required in all patients to ensure therapeutic levels are rapidly achieved. Up to 7.5 mg/kg may be required for serious infections and in neonates, but 2 mg/kg is sufficient for uncomplicated urinary tract infections and for synergistic therapy with penicillin for the treatment of streptococcal endocarditis. Serum concentrations of gentamicin must be measured during therapy to ensure efficacy and also to prevent toxicity due to unduly high levels, especially in renal failure and in the elderly. These measurements are usually carried out on two specimens of blood, the first taken 1 hour after a dose (peak) and the second just before the next dose (trough concentration). One-hour levels should be between 4 and 10 mg/l and trough levels less than 2 mg/l.

Tobramycin

This is more active than gentamicin against Ps. aeruginosa but has no other advantage.

Netilmicin

A gentamicin derivative, netilmicin is stable to three of nine aminoglycoside-inactivating enzymes, and should be reserved for infection caused by gentamicin-resistant organisms. Netilmicin is slightly less nephrotoxic than gentamicin, to which it is preferred in the elderly and if renal function is impaired.

Amikacin

This has less intrinsic antibacterial activity than gentamicin, but has the advantage of being stable to eight of the nine aminoglycoside-inactivating enzymes, in contrast to gentamicin which is susceptible to six of the nine. For this reason amikacin is active against many gentamicin-resistant Gram-negative bacilli and should be reserved for the treatment of infections caused by these organisms.

Neomycin

This is too toxic to be given parenterally but local applications containing neomycin are used in infections of the skin and eye. Neomycin may be used orally in hepatic encephalopathy to reduce the numbers of colonic bacteria.

The aminoglycosides are all nephrotoxic and ototoxic. The most common adverse effect of the aminoglycosides is on the 8th cranial nerve. Aminoglycosides, especially gentamicin, should not be administered together with the diuretic frusemide, as additive ototoxicity may result from the combination.

The toxicity of the aminoglycosides is related to the age of the patient, the serum level of the antibiotic and the duration of administration. The aminoglycosides are principally excreted from the body by the kidneys and the risk of toxicity is increased when there is impairment of renal function. Serum levels of the aminoglycosides must be measured in all patients to prevent toxicity and also to ensure therapeutic blood levels.

OTHER ANTIBIOTICS AND CHEMOTHERAPEUTIC AGENTS

Chloramphenicol

This has a range of activity similar to that of the tetracyclines, with the important difference that it is effective in enteric fever. It is more active than the tetracyclines against H. influenzae and is an antibiotic of choice in meningitis due to this organism, particularly in developing countries where cefotaxime may not be available. The daily oral dose for an adult is 1-3 g. Preparations for parenteral administration are also available and are particularly useful in severe infection in developing countries. Plasma levels resulting from intramuscular injections are equivalent to those resulting from intravenous route administration. Chloramphenicol eye drops and ointment are useful for purulent conjunctivitis.

Chloramphenicol has in its chemical structure a benzene ring of the type known to cause bone marrow aplasia. Although pancytopenia due to chloramphenicol is very uncommon, it is almost invariably a serious complication; this antibiotic should be used systemically only if there is no adequate alternative therapy. It is inexpensive and therefore used widely in developing countries. Chloramphenicol should never be given to premature infants or to the newborn because of the risk of the development of the frequently fatal "grey baby syndrome'. This is a state of acute circulatory failure caused by the very high blood levels of chloramphenicol due to its inadequate conjugation in the liver at this age.

Clindamycin (7-chlorolincomycin)

This has a similar antibacterial spectrum to penicillin against most Gram-positive organisms, including penicillin-resistant staphylococci. It penetrates well into bone and is therefore useful for osteomyelitis caused by Staph. aureus. The other principal indications are for the treatment of infections caused by B. fragilis and for lung abscess. The dose is 300 mg 6-hourly, orally or by injection.

Clindamycin is a common cause of antibiotic-associated colitis. This adverse reaction, which can also complicate treatment with other antibiotics, especially ampicillin, is due to selective overgrowth of Clostridium difficile which produces toxins detectable in faeces and are the direct cause of the disease. Treatment is with oral vancomycin or metronidazole, the latter being less costly.

Sodium fusidate

This is bactericidal against Staph. aureus and is useful in infections caused by penicillin-resistant staphylococci. The dose is 250-500 mg 8-hourly by mouth. Nausea and vomiting are common. An intravenous preparation is available: cholestatic jaundice has occasionally been associated with its use. It is expensive and is indicated only for serious infections due to staphylococci, especially osteomyelitis and endocarditis. The drug is very well absorbed and the oral route can be used instead of the parenteral route.

Spectinomycin

This is an aminocyclitol compound with a certain structural similarity to streptomycin, although it is not an aminoglycoside. Its only clinical use is for the treatment of gonorrhoea if penicillin is contraindicated because of allergy or bacterial resistance.

Vancomycin and teicoplanin

These are glycopeptide bactericidal antibiotics. Indications for their use are limited to serious infections such as endocarditis (treatment and prophylaxis) or septicaemia caused by Staph. aureus and Staph. epidermidis, including methicillin-resistant strains (MRSA and MRSE). Oral vancomycin (125 mg 6-hourly) is used for antibioticassociated colitis. Teicoplanin has a longer serum half-life than vancomycin and can therefore be given once daily.

Parenteral administration of vancomycin is by slow intravenous infusion of 500-1000 mg over 60 minutes 12hourly if renal function is normal. Plasma levels must be monitored-peak (1-hour) levels should not exceed 30 mg/l and pre-dose levels must not exceed 10 mg/l. Side-effects include fever, rash and, if plasma levels exceed recommended concentrations, nephrotoxicity and ototoxicity. The daily dose must be reduced in renal failure.

Sulphonamides

These have largely been superseded by antibiotics although their usefulness was extended by the discovery of their synergistic action with trimethoprim, dapsone and pyrimethamine. Co-trimoxazole, a preparation containing sulphamethoxazole and trimethoprim, is, however, active against a wide range of bacteria. Dapsone-sulphamethoxazole is used to treat malaria, and pyrimethamine-sulphamethoxazole to treat toxoplasmosis.

The sulphonamides most suitable for clinical use are short-acting preparations such as sulphadimidine, which is rapidly absorbed and quickly excreted in the urine in a soluble form. One of the few remaining indications for the

ADVERSE EFFECTS OF THE SULPHONAMIDES
Skin rash, including Stevens-Johnson syndrome (erythema multiforme and mucous membrane ulceration) Drug fever Blood dyscrasias including haemolysis in glucose-6 phosphate deficiency Nephritis Photosensitivity (topical use) Interaction with warfarin and sulphonylurea drugs

sulphonamides is cystitis. However, the use of double-dose co-trimoxazole is a first-line treatment for Pneumocystis carinii pneumonia in immunocom hosts,e.g. HIV. Sulphonamides have a wide range of potential hazards .

Co-imoxazole

This consists of trimethoprim and sulphamethoxazole, which act by inhibiting enzymes at two successive stages in the enthesis of para-aminobenzoic acid to folic acid and DNA Co-trimoxazole is used for treatment of exacerbations of chronic bronchitis and urinary tract infections . It is also effective in the treatment of invasive salmonella infections . The adult dose is two tablets (each containing 80 mg of trimethoprim and 400 mg of sulphamethoxazole) given 12-hourly by mouth. There is also a preparation for injection.

The adverse effects are those of the sulphonamides . Stevens-Johnson syndrome has been reported in association with co-trimoxazole. In addition, haematological reactions to trimethoprim, including thrombocytopenia and megaloblastic anaemia, may occur due to folate deficiency. Side-effects are most common in the elderly, in whom co-trimoxazole should be avoided.

Trimethoprim

On its own this is used for the treatment of urinary tract infection in a dose of 200 mg 12-hourly, or 100 mg each evening for long-term chemoprophylaxis. It is also used for the treatment of respiratory tract infections. Side-effects are fewer than with co-trimoxazole, especially in the elderly.

Nalidixic acid

This was the first 4-quinolone to be introduced, 30 years ago. These agents are inhibitors of DNA gyrase, the enzyme responsible for supercoiling of bacterial DNA. While nalidixic acid has only modest antibacterial activity and is poorly Osorbed from the gut, several new 4-quinolones have been have been developed with significantly greater activity and improved absorption.

Ciprofloxacin

This is the most important of the new 4-quinolones. It has a relatively broad spectrum with particularly high activity against aerobic Gram-negative bacilli including salmonellae, shigellae, Campylobacter and Pseudomonas species. It is also active against chlamydiae and mycoplasmas but not against anaerobic bacteria. Although many Gram-positive organisms are sensitive to ciprofloxacin, the activity is only moderate, especially against pneumococci. Ciprofloxacin diffuses readily into infected tissues and cells. The oral dose is 250-750 mg 12-hourly and for intravenous infusion 200 mg 12-hourly.

Ciprofloxacin has a wide range of indications including gastrointestinal, urinary tract and lower respiratory tract infections (not pneumococcal), septicaemia and gonorrhoea.

Indications for the other available 4.quinolones are listed in the first information box With the exception of ciprofloxacin which has an oral and intravenous formulation, they are given orally. The adverse reactions encountered with the 4.quinolones are summarised in the second information boxNewer quinolones will be available with a wider antimicrobial spectrum.

INDICATIONS FOR THE USE OF THE 4-QUINOLONE ANTIBIOTICS
Treatment of gonorrhoea
Acrosoxacin (300 mg single dose)
Treatment of urinary tract infections
Nalidixic acid (1 g 6-hourly) Norfloxacin (400 mg 12-hourly) Cinoxacin (500 mg 12-hourly)
Broad-spectrum
Ofloxacin (UTI, LRTI, STD) (200-400 mg daily) Ciprofloxacin (UTI, LRTI, STD, GI infections, typhoid fever, septicaemia, meningococcal prophylaxis) (see text for dose)
All given orally, ciprofloxacin also available for i.v. injection (UTI = urinary tract infection; LRTI = lower respiratory tract infection but not pneumococcal; STD = sexually transmitted disease; GI = gastrointestinal)

ADVERSE EFFECTS OF 4-QUINOLONES
Gastrointestinal
Nausea Vomiting Diarrhoea
Rashes
Maculo-papular Photosensitivity Urticaria
Neurotoxicity
Insomnia Dizziness Headache Convulsions (rare)
Drug interactions
NSAIDs Theophylline Peptic ulcer drugs
Note 4-quinolones are contraindicated in children and pregnancy (arthropathy in young animals).

Metronidazole

This imidazole compound has high activity against anaerobic bacteria and intestinal protozoa but none against aerobic bacteria. It is effective against infection due to Trichomonas iginalis, Giandia lamblia and Entamoeba histolytica, and is widely used for the treatment and prophylaxis of infections caused by anaerobic bacteria, notably B. fragilis. It is active against Clostridium tetani and Cl difficile. Side-effects of metronidazole are usually limited to headache and nausea but it should not be given to women during the first trimester of pregnancy as fetal abnormalities have been reported in animals given high doses for prolonged periods. Alcohol should be avoided during therapy with metronidazole, which has a similar action to disulfiram and has an Antabuse-like effect (nausea, lightheadedness). The oral dose varies from 200-400 mg 8-hourly: 800 mg 8-hourly is required for intestinal amoebic infections. There are preparations for intravenous infusion and rectal use.

Tinidazole

This is similar to metronidazole but has a longer serum half-life (12 hours as compared to 7 hours), allowing less frequent administration, and is less toxic.

Mupirocin

This is not related to any other antibiotic and is only indicated for application to the skin or anterior nose for the treatment of skin infection or eradication of staphylococcal carriage.