kucers’ the use of antibiotics (7/e): part 2

2:11 QUINOLONES AND<br /> FLUOROQUINOLONES<br /> <br /> 2:11A New and Commonly Used<br /> Fluoroquinolones<br /> <br /> 101<br /> Ciprofloxacin<br /> Jason Kwong and M. Lindsay Grayson<br /> <br /> 1. DESCRIPTION<br /> Ciprofloxacin is a fluoroquinolone (also called 4-quinolone,<br /> or quinolone carboxylic acid) that was developed by Bayer<br /> Pharmaceuticals for both oral and parenteral use. It is one of<br /> the second generation of quinolones (others include norfloxacin, ofloxacin, pefloxacin, and enoxacin) that have substantially enhanced antibacterial activity, compared for example<br /> with nalidixic acid (the first quinolone antibiotic). Ciprofloxacin, previously known as Bay 09867, is chemically known as<br /> 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)<br /> 3-quinolone carboxylic acid hydrochloride (Wise et al., 1983),<br /> has the empirical formula C17H18FN3O3 and its molecular<br /> weight is 331.34. The chemical structure is shown in Figure 101.1.<br /> Although developed after norfloxacin, successful widespread clinical experience with ciprofloxacin has resulted in<br /> it being regarded as the classic fluoroquinolone, against<br /> which other later generation quinolones are to be compared.<br /> Similar to most other second-generation quinolones, it has a<br /> long half-life, allowing twice daily dosing and good penetration into human cells, thereby providing good activity against<br /> intracellular pathogens. It has good tissue penetration and<br /> high potency against most Gram-negative pathogens, with<br /> lesser activity against staphylococci, and borderline or poor<br /> activity against streptococci and anaerobes. In general, ciprofloxacin has 2- to 4-fold greater antimicrobial potency than<br /> norfloxacin, and considerably greater in vitro activity than<br /> cephalosporins and aminoglycosides against most Gram-<br /> <br /> NH<br /> N<br /> HO<br /> <br /> N<br /> <br /> F<br /> O<br /> <br /> O<br /> <br /> Figure 101.1. Chemical structure of ciprofloxacin.<br /> <br /> negative bacilli (Sanders et al., 1987; Hooper and Wolfson,<br /> 1993a; Moellering, 1993). Neu (1989a) and Mitscher et al.<br /> (1993) have extensively reviewed the relationship between<br /> quinolone structure and in vitro activity.<br /> The generally excellent oral absorption of ciprofloxacin<br /> means that in higher oral doses, serum levels can be achieved<br /> with oral therapy similar to those achieved with intravenous<br /> dosing, such that (assuming normal gastrointestinal absorption) oral ciprofloxacin provides “IV-equivalent” therapy for<br /> many non-neurological infections, similar to chloramphenicol (see Chapter 86, Chloramphenicol and Thiamphenicol),<br /> doxycycline (see Chapter 68, Doxycycline) and metronidazole (see Chapter 99, Metronidazole). Given the classic status<br /> of ciprofloxacin, most features that fluoroquinolones have in<br /> common will be discussed in this chapter.<br /> Oral preparations consist of ciprofloxacin hydrochloride<br /> tablets in 250, 500, or 750 mg doses; there are 500 and 1000<br /> mg extended release tablets in some countries. Microcapsules<br /> are available in concentrations of 250 and 500 mg/5 ml and<br /> can be used as a suspension for children. Pharmacies will<br /> frequently be able to prepare a suspension—typically in a<br /> 100 ml bottle with a concentration of 50 mg/ml. Solutions<br /> and ointments for topical (ophthalmic) use contain a 0.3%<br /> base; 2 mg in 10 ml ear drops are also available. Parenteral<br /> preparations for infusion contain 100, 200, or 400 mg; injection solutions contain 10 mg/ml. Formulations and availability will vary between different countries.<br /> <br /> 2. ANTIMICROBIAL ACTIVITY<br /> 2a. Routine susceptibility<br /> GRAM-NEGATIVE AEROBIC BACTERIA<br /> <br /> Ciprofloxacin has excellent activity against the vast majority<br /> of Enterobacteriaceae (see Table 101.1), such as Escherichia<br /> coli and the Enterobacter, Klebsiella, Proteus, Morganella,<br /> Edwardsiella, Providencia, Citrobacter, and Serratia species.<br /> Although it is more active than most other similar antimicrobial agents (Auckenthaler et al., 1986; Samonis et al.,<br /> 1867<br /> <br />