Antimicrobial Chemotherapy, 5th Edition

Part 1 - General Properties of Antimicrobial Agents

Chapter 3

Synthetic Antibacterial Agents and Miscellaneous Antibiotics

Various targets other than the cell wall and ribosome are open to attack by chemotherapeutic agents. This chapter describes the properties of inhibitors of bacterial nucleic acid synthesis, compounds that act on the bacterial cell membrane, and agents used solely for the treatment of mycobacterial disease. Many of these compounds are synthetic chemicals rather than antibiotics in the strict sense.

Inhibitors of nucleic acid synthesis

Given the universality of nucleic acid as the basis of life, it is surprising that so many antimicrobial agents have been discovered that selectively interfere with the functions of DNA and RNA. Some, like the sulphonamides and diaminopyrimidines, achieve their effect indirectly by interrupting metabolic pathways that lead to the manufacture of nucleic acids; others, of which the quinolones and nitroimidazoles are prime examples, exert a more direct action.

Sulphonamides: Mostly obsolete

The discovery of Prontosil in the 1930s was a major breakthrough in the chemotherapy of bacterial infections (see Historical introduction). Activity of the dye is due to the liberation in the body of sulphanilamide, an analogue of para-aminobenzoic acid (Fig. 3.1), which is essential for bacterial folate synthesis. Most bacteria synthesize folic acid and cannot take it up preformed from the environment. Mammalian cells, in contrast, use preformed folate and cannot make their own. Sulphonamides block an early stage in folate synthesis leading to various effects, including a failure to synthesize purine nucleotides and thymidine. Chemical modification of the sulphanilamide molecule has resulted in the production of hundreds of different sulphonamides, which differ chiefly in their pharmacological properties.

Sulphonamides have a broad antibacterial spectrum, though the activity against enterococci, Pseudomonas aeruginosa, and anaerobes is poor. They are predominantly bacteristatic, and relatively slow to act: several generations of bacterial growth are needed to deplete the folate pool before inhibition of growth occurs. Resistance emerges readily, and bacteria resistant to one sulphonamide are cross-resistant to the others. Sensitivity tests present problems in the laboratory since results depend critically on the composition of the culture medium and the inoculum size.

 

Fig. 3.1 Structures of prontosil, sulphanilimide, and p-aminobenzoic acid.

The emergence of resistant strains and the appearance of safer and more potent agents have relegated the sulphonamides to a minor place in therapy. Even in their traditional role, uncomplicated urinary infection, they are now seldom used. They are still found in combination products with trimethoprim, pyrimethamine, and other diaminopyrimidines (see below).

Topical silver sulfadiazine is used in burns, but the activity probably owes as much to the silver as to the sulphonamide. In curious extension of the good fortune that attended the discovery of the sulphonamides, sulfasalazine, an agent used in ulcerative colitis and rheumatoid arthritis, probably owes its efficacy to a breakdown product, 5-aminosalicylic acid.

Most sulphonamides are well absorbed when given orally and are chiefly excreted in the urine, partly in an antibacterially inactive acetylated form. The compounds diffuse relatively well into cerebrospinal fluid and were successfully used for treating meningitis before resistance became common. Sulfadiazine is effective in eradicating Neisseria meningitidis from the throat, provided the strain is not sulphonamide resistant.

Less soluble sulphonamides (e.g. sulfathiazole and sulfadiazine) are prone to cause renal damage due to the deposition of crystals in the urinary collecting system. Sulfafurazole (known as sulfisoxazole in the USA), sulfadimidine (sulfamethazine), sulfasomidine (sulfisomidine), and sulfamethizole lack this side effect and are preferred in the treatment of urinary infection. Some sulphonamides are distinguished by long plasma half-lives (T½) and are known as long-acting sulphonamides. Sulfametopyrazine (T½ = 60 h) and sulfadoxine (T½ = 120h) are excreted so slowly that they are given at weekly intervals.

Diaminopyrimidines

Diaminopyrimidines inhibit dihydrofolate reductase, the enzyme that generates tetrahydrofolate (the active form of the vitamin) from metabolically inactive dihydrofolate. Trimethoprim (Fig. 3.2), the most important antibacterial agent of this type, exhibits far greater affinity for the dihydrofolate reductase of bacteria than for the corresponding mammalian enzyme; this is the basis of the selective toxicity of the compound.

Since sulphonamides and trimethoprim act at different points in the same metabolic pathway they interact synergically: bacteria are inhibited by much lower concentrations of the combination than by either agent alone. For this reason trimethoprim and sulphonamides are often combined in therapeutic formulations, although trimethoprim alone is probably as effective and less toxic. The most commonly used combination is trimethoprim and sulfamethoxazole (co-trimoxazole), but combinations of trimethoprim with sulfadiazine (co-trimazine) and sulfamoxole (co-trifamole) are also available in some countries.

Trimethoprim is active in low concentration against many common pathogenic bacteria, although Ps. aeruginosa is a notable exception. Resistance is on the increase; over 30% of urinary isolates have been reported to be resistant in some series, but this is not a universal experience. The drug is rapidly absorbed from the gut and excreted almost exclusively by the kidneys with a plasma half-life of about 10 h.

The chief use for trimethoprim is in urinary tract infection. The combination with sulfamethoxazole is principally used in pneumonia caused by the fungus, Pneumocystis carinii (P. jiroveci; see p. 73). It has also been extensively used in many other clinical situations, including typhoid fever, and brucellosis. Although toxic side effects are uncommon, trimethoprim-sulphonamide combinations are prone to rare, but severe side effects (see p. 228) and it is preferable to use trimethoprim alone wherever possible.

 

Fig. 3.2 Structure of trimethoprim.

Analogues of trimethoprim, including tetroxoprim and brodimoprim, are marketed in combination with sulphonamides in some countries, but offer few, if any advantages. Other diaminopyrimidines include the antimalarial agents pyrimethamine and proguanil (Chapter 5); the anti-pneumocystis agent trimetrexate; and the antineoplastic agent methotrexate.

Quinolones

Nalidixic acid (Fig. 3.3) was the first representative to appear of a family of compounds that share close similarities of structure. These agents are generically known as quinolones, although they embrace a variety of molecular types, depending on the arrangement of nitrogen atoms within the heterocyclic structure.

Among the earlier quinolones are two with modestly improved antibacterial activity: flumequine (which bears a fluorine atom at the C-6 position) and pipemidic acid (with a piperazine substituent at C-7). During the 1980s a new series of quinolones were synthesized in which these two features were combined. These compounds, of which ciprofloxacin (Fig. 3.3) is a typical example, exhibit considerably enhanced activity. In some subsequent derivatives, piperazine was replaced by other substituents, and members of this family of compounds are now generally referred to as fluoroquinolones. Although flumequine is strictly a fluoroquinolone, the term is usually restricted to compounds that exhibit superior intrinsic activity.

Further attempts to improve the pharmacological and antimicrobial properties of these compounds have led to the appearance of a new group of fluoroquinolones, so that these agents can now be loosely categorized into three types (Table 3.1).

 

Fig. 3.3 Structures of nalidixic acid and ciprofloxacin.

 

Table 3.1 Categorization of quinolone antibacterial agents

Narrow spectrum quinolones

Fluoroquinolones

Fluoroquinolones with improved spectrum

Acrosoxacin

Ciprofloxacina

Clinafloxacin

Cinoxacin

Enoxacin

Gatifloxacin

Flumequine

Fleroxacin

Gemifloxacin

Nalidixic acida

Levofloxacina

Moxifloxacina

Oxolinic acid

Lomefloxacin

Pazufloxacin

Pipemidic acid

Norfloxacina

Sparfloxacin

Piromidic acid

Ofloxacina

Tosufloxacin

 

Pefloxacin

Trovafloxacin

 

Rufloxacin

 

Compounds on the market in the UK (2006).

All antibacterial quinolones act against the remarkable enzymes that are involved in maintaining the integrity of the supercoiled DNA helix during replication and transcription. Two enzymes are affected, DNA gyrase and topoisomerase IV, so that these drugs have a dual site of action. In Gram-negative bacilli the main target is DNA gyrase, with topoisomerase IV as a secondary site, but in Staphylococcus aureus and some other Gram-positive cocci, the situation is reversed. Relative affinity for the two sites has led to claims of differential activity, especially among some of the newer quinolone derivatives.

Quinolones are generally well tolerated, but rashes and gastrointestinal disturbances may occur; photophobia and various non-specific neurological complaints are also sometimes encountered. These compounds affect the deposition of cartilage in experimental animals, and licensing authorities have cautioned against their use in children and pregnant women. Several promising fluoroquinolones have had to be withdrawn or have had their use restricted because of unexpected toxicity.

Nalidixic acid and its early congeners: Uncomplicated cystitis only

Several quinolone derivatives, including cinoxacin, oxolinic acid, and pipemidic acid, were introduced into clinical use in various countries following the marketing of nalidixic acid in the 1960s (Table 3.1, left-hand column). They are all well absorbed when taken by mouth and are more or less extensively metabolized in the body before being excreted into the urine. Nalidixic acid itself is largely converted to hydroxynalidixic acid (which retains antibacterial activity) and glucuronide conjugates (which do not).

Most Gram-negative bacteria, with the exception of Ps. aeruginosa, are susceptible to nalidixic acid and its early congeners, but Gram-positive organisms are usually resistant (Table 3.2). Susceptible bacteria readily develop resistance in the laboratory and the emergence of resistance sometimes occurs during treatment. These drugs are best suited to the undemanding role of the treatment of cystitis, though they are also used in gastrointestinal disease in some parts of the world. Acrosoxacin exhibits good activity against Neisseria and has been used for the treatment of gonorrhoea. These older quinolones offer few benefits and only nalidixic acid remains widely available.

Fluoroquinolones

After the appearance, over a 20-year period, of a series of compounds that offered little improvement over nalidixic acid, the discovery of a family of quinolones that exhibited greatly improved properties came as a surprise. These compounds, listed in the central column of Table 3.1, are much more active than earlier derivatives against enterobacteria, Ps. aeruginosa, and many Gram-positive cocci (Table 3.2), though the activity is somewhat reduced in acidic conditions and in the presence of divalent cations such as magnesium. The spectrum also includes certain problem organisms such as chlamydiae, legionellae, and some mycobacteria. Similar compounds, including enrofloxacin, danofloxacin, and sarafloxacin, have been introduced into veterinary practice and there has been considerable debate about the impact this may have had on the development of resistance.

The success of the first fluoroquinolones led to an intensive search for derivatives with further improved properties and this has borne fruit with several new agents now on the world market, or at an advanced stage of development (Table 3.1, right-hand column). These compounds are characterized by enhanced activity against Gram-positive cocci, including Staph. aureus and Streptococcus pneumoniae as well as chlamydiae and mycoplasmas; clinafloxacin, gatifloxacin, moxifloxacin, and trovafloxacin also have sufficient activity against anaerobes of the Bacteroides fragilis group to make treatment of infections with those organisms feasible. They are not reliably active against Ps. aeruginosa.

Fluoroquinolones are usually administered orally, although some, including ciprofloxacin, ofloxacin, levofloxacin (the L-isomer of ofloxacin), and trovafloxacin (in the form of its pro-drug, alatrofloxacin), can also be given by injection. Therapeutic dosages achieve relatively low concentrations in plasma, but the compounds are well distributed in tissues and are concentrated within mammalian cells. The major route of excretion is usually renal, in the form of native compound or glucuronide and other metabolites, some of which retain antibacterial activity. Some fluoroquinolones, notably rufloxacin and sparfloxacin, but also including moxifloxacin, and trovafloxacin, exhibit long terminal half-lives; these compounds are partly excreted by the biliary route and this may help to explain the long half-life.

 

Table 3.2 Summary of spectrum of activity of quinolones available in the UK (2006)

Quinolone

Enterobacteria

Pseudomonas aeruginosa

Staphylococci

Streptococci

Bacteroides fragilis

Chlamydiae

Ciprofloxacin

Very good

Good

Good

Fair

Poor

Poor

Levofloxacin

Very good

Good

Good

Fair

Fair

Good

Moxifloxacin

Very good

Poor

Very good

Good

Fair

Good

Nalidixic acid

Good

Poor

Poor

Poor

Poor

Poor

Norfloxacin

Very good

Good

Fair

Poor

Poor

Poor

Ofloxacin

Very good

Good

Fair

Fair

Poor

Fair

 

Among currently available fluoroquinolones, norfloxacin, enoxacin, and lomefloxacin have found their greatest use as more reliable replacements for earlier derivatives in the treatment of urinary tract infection, though they may also have wider uses, for example in gonococcal and gastrointestinal infections. Others are used for systemic infection and have become the subject of conflicting marketing claims. Ciprofloxacin is the most widely used; among other indications, it is now the drug of choice for typhoid fever and other serious enteric diseases. The ease of administration of fluoroquinolones makes them attractive candidates for ‘blind’ therapy in hospital and domiciliary practice. However, they are not universal panaceas and should not be used indiscriminately. The newer derivatives are being targeted at the treatment of respiratory infections in the community and, although they are undoubtedly effective, it is not clear that such use is necessary or wise. Indeed, there is already evidence that indiscriminate use of fluoroquinolones is undermining the effectiveness of these valuable drugs by encouraging resistance, notably in Gram-negative bacilli and pneumococci.

Nitroimidazoles: Anaerobic infections only

As a group, the imidazoles are remarkable in that derivatives are known, which between them cover bacteria, fungi, viruses, protozoa, and helminths—in fact, the whole antimicrobial spectrum. Outside the antimicrobial field certain imidazoles have been shown to exhibit radiosensitizing properties and have attracted attention as adjuncts to radiation therapy for some tumours.

The members of this family of compounds used as antibacterial agents are 5-nitroimidazoles, of which metronidazole (Fig. 3.4) is best known. Related 5-nitroimidazoles include tinidazole, ornidazole, secnidazole, and nimorazole; they share the properties of metronidazole but have longer plasma half-lives.

 

 

Fig. 3.4 Structure of metronidazole.

Metronidazole was originally used for the treatment of trichomoniasis, and subsequently for two other protozoal infections—amoebiasis and giardiasis. The antibacterial activity of the compound was first recognized when a patient suffering from acute ulcerative gingivitis responded spontaneously while receiving metronidazole for a Trichomonas vaginalis infection. Anaerobic bacteria are commonly incriminated in gingivitis, and it was subsequently shown that metronidazole possesses potent antibacterial activity that was originally thought to be confined to strict anaerobes (the protozoa against which the drug is effective also exhibit anaerobic metabolism) since even oxygen-tolerant species such as Actinomyces and Propionibacterium are resistant. However, some micro-aerophilic bacteria, including Gardnerella vaginalisand Helicobacter pylori, are commonly susceptible to nitroimidazoles, and metronidazole features in drug regimens for the treatment of infections with these organisms.

Metronidazole is so effective against anaerobic bacteria and resistance is so uncommon that it is now the drug of choice for the treatment of anaerobic infections. It is also commonly used for prophylaxis in some surgical procedures in which postoperative anaerobic infection is a frequent complication. It is the preferred alternative to vancomycin in the treatment of antibiotic-associated colitis caused by Clostridium difficile toxins (p. 303).

The basis of the selective activity against anaerobes resides in the fact that a reduction product is produced intracellularly at the low redox values attainable by anaerobes, but not by aerobes. The reduced form of metronidazole is thought to induce strand breakage in DNA by a mechanism that has not been precisely determined.

The 5-nitroimidazoles are generally free from serious side effects, though gastrointestinal upset is common and ingestion of alcohol induces a disulfiram-like reaction. Since these drugs act on DNA they are potentially genotoxic and tumorigenic, but there is no evidence that these problems have arisen despite widespread clinical use. None the less, these compounds are best avoided in pregnancy.

 

Nitrofurans: Urinary tract infection only (nitrofurantoin)

A number of nitrofuran derivatives have attracted attention over the years, among which nitrofurantoin (Fig. 3.5) is much the most important. Others include furazolidone (an orally compound sometimes used for intestinal infections); nitrofurazone (a topical agent also used for bladder irrigation); nifuratel and nifuroxime (used in some countries for T. vaginalis infection and vaginal thrush); and nifurtimox (used in Chagas' disease; see p. 429).

 

Fig. 3.5 Structure of nitrofurantoin.

Nitrofurantoin is the only nitrofuran derivative available in the UK. Its use is restricted to the treatment of urinary infection since it is rapidly excreted into urine after oral absorption and the small amount that finds its way into tissues is inactivated there. It is active against most urinary tract pathogens, but Proteus spp. and Ps. aeruginosa are usually resistant. The occurrence of resistant strains among susceptible species is uncommon. The activity is affected by pH, being favoured by acid conditions.

Nausea is fairly common after administration of nitrofurantoin; macrocrystalline formulations have improved gastrointestinal tolerance and are generally preferred for this reason.

The mode of action of nitrofurantoin (or other nitrofurans) has not been precisely elucidated and is probably complex. The nitro group is reduced intracellularly in susceptible bacteria and it is likely that one effect, as with metronidazole, is the interaction of a reduction product with DNA.

Rifamycins: Mainly mycobacterial infections

The clinically useful rifamycins, of which rifampicin (known in the USA as rifampin) is the most important, are semisynthetic derivatives of rifamycin B, one of a group of structurally complex antibiotics produced by Streptomyces mediterranei. These compounds interfere with mRNA formation by binding to the β-subunit of DNA-dependent RNA polymerase. Resistance readily arises by mutations in the subunit. For this reason, the drugs are normally used in combination with other agents.

Rifampicin

Rifampicin is one of the most effective weapons against two major mycobacterial scourges of mankind: tuberculosis and leprosy. It also exhibits potent bactericidal activity against a range of other bacteria, notably staphylococci and legionellae. Rifampicin is such a useful antimycobacterial drug that there has been a move to confine its use to tuberculosis and leprosy on the grounds that more widespread use might inadvertently encourage the emergence of resistant strains of mycobacteria. Critics of this view claim that an agent that possesses exceptionally good antistaphylococcal activity and useful activity against other bacteria is being unnecessarily restricted on unproven grounds. In fact, restriction of the use of rifampicin has been steadily eroded: it is now often used in combination with erythromycin in Legionnaires' disease; it is also used to eliminate meningococci from the throats of carriers and for the protection of close contacts of meningococcal and Haemophilus influenzae type b disease.

Rifampicin is well absorbed by the oral route, although it may also be given by intravenous infusion. Serious side effects are relatively uncommon, but can be more troublesome when the drug is used intermittently, as it may be in antituberculosis regimens. Hepatotoxicity is well recognized and the antibiotic induces hepatic enzymes, leading to self-potentiation of excretion and antagonism of some other drugs handled by the liver, including oral contraceptives. A potentially alarming side effect arising from the fact that rifampicin is strongly pigmented is the production of red urine and other bodily secretions; contact lenses may become discoloured. Patients should be warned of these potential problems.

Other rifamycins

Two other rifamycin derivatives are of particular interest: rifapentine exhibits an extended plasma half-life, but is otherwise similar to rifampicin; rifabutin (ansamycin) also has a prolonged half-life and retains activity against some rifampicin-resistant bacteria. Much interest has focused on the possibility that these agents may be useful in infections caused by organisms of the Mycobacterium avium complex, which often cause disseminated disease in patients with cancer or acquired immune deficiency syndrome (AIDS). Although these mycobacteria are commonly resistant to standard antituberculosis drugs, rifabutin and rifapentine display good activity in vitro. Clinical success has been modest, but rifabutin has proved of sufficient value to warrant its inclusion in some multidrug regimens for prophylaxis against infection with organisms of the M. avium complex.

Rifaximin, rifamide, and rifamycin SV are poorly absorbed after oral administration. Although they are marketed in some countries for gastrointestinal infections and for topical application, they are not recommended.

 

Agents affecting membrane function

Polymyxins: Pseudomonas infections only

The polymyxins are a family of compounds produced by Bacillus polymyxa and related bacteria. Only polymyxins B and E are used therapeutically. Polymyxin E is usually known by its alternative name, colistin. Structurally, the polymyxins are cyclic polypeptides with a long hydrophobic tail. They act like cationic detergents by binding to the cell membrane and causing the leakage of essential cytoplasmic contents. The effect is not entirely selective, and both polymyxin B and colistin exhibit considerable toxicity.

Derivatives of the polymyxins in which up to five diaminobutyric acid residues are substituted with sulphomethyl groups are better tolerated and more quickly excreted than the parent compounds. These sulphomethyl polymyxins exhibit diminished antibacterial activity, but the precise loss in activity is difficult to estimate because the substituted compounds spontaneously break down to the more active parent.

The antibacterial spectrum of the polymyxins encompasses most Gram-negative bacteria except Proteus spp., but the importance of these antibiotics hinges on their activity against Ps. aeruginosa. With the appearance of antipseudomonal β-lactam agents, aminoglycosides, and fluoroquinolones, the polymyxins have virtually fallen into disuse for systemic therapy, although they are still used in some topical preparations. They are also included in selective decontamination regimens aimed at preventing endogenous infection in profoundly neutropenic patients (p. 403) and there are advocates of the use of colistin in cystic fibrosis by instillation into the lungs of those suffering exacerbation of pseudomonal infection.

Other membrane-active agents

Daptomycin, a semi-synthetic lipopeptide antibiotic not unlike the polymyxins in structure, has various effects on bacteria, but the primary mode of action is thought to lie in disruption of the cell membrane. Development of the compound in the 1980s was stopped because of fears of toxicity, but the rise to prominence of multiresistant Gram-positive cocci revived commercial interest and it is now marketed for serious infections of the skin and soft tissues that are unresponsive to other agents, especially those caused by multiresistant staphylococci. Activity is restricted to Gram-positive cocci and is greatly enhanced in vitro by the presence of magnesium ions.

Antibiotics of the tyrothricin complex (gramicidin and tyrocidine), which are used in some topical preparations, are cyclic peptides that bind to the cell membrane and interfere with its function. These agents possess good activity against Gram-positive organisms, but they also bind to mammalian cell membranes and are far too toxic to be used systemically in humans.

Toxicity also precludes the systemic use of the many disinfectants, including phenols, quaternary ammonium compounds, biguanides, and others, that achieve their antibacterial effect wholly or in part by interfering with the integrity of the cell membrane.

Naturally occurring oligopeptides that destabilize bacterial membranes are widespread in nature, where they play a part in innate defence against microbial infection. Compounds of this type include cecropins (originally described in insects), magainins (from frogs), defensins (from mammalian leucocytes), and lanthionine-containing ‘lantibiotics’ (from bacteria). Whether these, or related synthetic compounds, have any future as therapeutic agents remains to be seen.

Antimycobacterial agents

Compared with the number of agents at the disposal of the prescriber for the therapy of most bacterial infections, the resources available to treat mycobacterial disease are precariously meagre. Part of the reason is that mycobacteria are unusual organisms with a relatively impermeable waxy coat, but the fact that they are very slow growing and are able to survive and multiply within macrophages and necrotic tissue also makes them difficult targets.

In general, the development of drugs for the treatment of tuberculosis and leprosy has evolved along specialized lines, but some important antimycobacterial agents, such as rifampicin (see above) and certain aminoglycosides (Chapter 2), have wider uses. Agents specifically used for the treatment of tuberculosis include isoniazid (isonicotinic acid hydrazide), pyrazinamide, ethambutol, and thiacetazone (thioacetazone). Para-aminosalicylic acid, which was formerly much used in antituberculosis regimens, is no longer recommended, but this and other compounds with activity against Mycobacterium tuberculosis, such as capreomycin, cycloserine, and viomycin, may be considered if first-line treatment fails. In leprosy, the most important agents (apart from rifampicin) are dapsone (or its pro-drug, acedapsone) and clofazimine. The thioamides ethionamide and protionamide (prothionamide) are sometimes used, but are hepatotoxic.

Some fluoroquinolones and macrolides display quite good activity against mycobacteria, including M. leprae and organisms of the M. aviumcomplex, and these agents widen the options for treating mycobacterial disease at a time when resistance is emerging as a serious problem.

 

Because of the difficulties in studying mycobacteria in the laboratory, less is known about the mode of action of antimycobacterial drugs than about other antibacterial agents. Various theories have been put forward to explain the action of isoniazid. The most widely held view is that an oxidized product inhibits the formation of the mycolic acids that are peculiar to the cell walls of acid-fast bacilli. Other derivatives of nicotinic acid, including pyrazinamide, ethionamide, and protionamide, may act in the same way. Ethambutol probably inhibits the formation of arabinogalactan, a polysaccharide component of the mycobacterial cell wall. Dapsone (diaminodiphenyl sulphone) and para-aminosalicylic acid are related to the sulphonamides and have been assumed to share the same mode of action, but this is by no means certain. The mode of action of the antileprosy agent clofazimine has not been determined, but it may, like rifampicin, inhibit DNA-dependent RNA polymerase. Some puzzling aspects of the idiosyncratic spectrum of antimycobacterial agents may be explained by differences in uptake into susceptible cells.

Further information on these agents is given in the context of their use in Chapter 25.

Miscellaneous antibacterial agents: prescriber's survival kit

  • Trimethoprim: use alone for uncomplicated cystitis
  • Ciprofloxacin: good general purpose fluoroquinolone. Do not use in pneumococcal pneumonia
  • Norfloxacin: useful for uncomplicated cystitis
  • Metronidazole: drug of choice for anaerobic infections
  • Rifampicin: essential component of regimens for treatment of tuberculosis and leprosy