4.6 Fluoroquinolones

Non-fluorinated quinolones are no longer recommended because of their poor antibacterial activity. According to the Paul Ehrlich Society for Chemotherapy, the fluoroquinolones are classified into four groups, based on their spectrum of activity, their pharmacokinetics and indications (Table 21).

Table 22: Classification of fluoroquinolones (modified according to the Paul Ehrlich Society for Chemotherapy [3])

Generic name	Trade name*	Features of the group
Group 1	Norfloxacin Pefloxacin	• Indications essentially limited to UTIs in some countries, e.g. Germany. In France and other countries, pefloxacin is also available for systemic use.
Group 2	Enoxacin Fleroxacin** Ofloxacin Ciprofloxacin	• Broad indications for systemic use.
Group 3	Levofloxacin Sparfloxacin	• Improved activity against Gram-positive and 'atypical' pathogens
Group 4	Gatifloxacin Moxifloxacin	• Improved activity against Gram-positive and 'atypical' pathogens and anaerobes

UTI = urinary tract infections.

*Listed according to increasing in vitro activity (minimum inhibitory concentration) against indicative pathogens.

**lnvestigated in acute exacerbations of chronic bronchitis, UTIs, gonorrhoea and gastrointestinal infections.

The indication of Group 1 fluoroquinolones is limited to UTIs in some countries, e.g. Germany. In France and some other countries pefloxacin is also used for systemic oral and parenteral use. Norfloxacin is not available as parenteral antibiotic.

Group 2 fluoroquinolones includes fluoroquinolones for systemic use with a broad spectrum of indications. These include infections of the urinary tract, the respiratory tract, the skin and soft tissues, bones, joints as well as systemic infections and even sepsis. Group 2 fluoroquinolones exhibit good activity against Enterobacteria and H. influenzae with less activity against staphylococci, pneumococci and enterococci as well as the 'atypical' pathogens, e.g. Chlamydia, Legionella and Mycoplasma. Their activity against P. aeruginosa varies, with ciprofloxacin being most active in vitro. In addition, ciprofloxacin, ofloxacin and fleroxacin are also available for parenteral use.

The spectrum of activity of Group 3 fluoroquinolones (levofloxacin and sparfloxacin) and of Group 4 fluoroquinolones differs from that of Group 2 quinolones mainly in that they have a higher intrinsic activity against Gram-positive pathogens such as staphylococci, streptococci, pneumococci and enterococci - with comparable activity against Gram-negative pathogens. In addition, they have improved activity against the so-called 'atypical' pathogens, such as Chlamydia, Mycoplasma and Legionella spp. In addition, Group 4 fluoroquinolones have improved anti-anaerobic activity. The only Group 3 fluoroquinolone available for parenteral use is levofloxacin, the left-enantiomer of the ofloxacin racemate. Grouping of levofloxacin is contradictory, because levofloxacin is the antibacterially active part of ofloxacin, which belongs to Group 2. The main indications for levofloxacin are respiratory tract infections, and, due to its high renal elimination rate, UTIs, as well as skin and soft-tissue infections.

Among Group 4 fluoroquinolones, gatifloxacin, moxifloxacin and trovafloxacin have been licensed. However, in June 1999, trovafloxacin was taken off the market because of severe side effects. Thus, so far, no parenteral fluoroquinolone of this group is available. Apart from respiratory tract infections, these broad-spectrum fluoroquinolones are appropriate for the treatment of skin and soft-tissue infections, of intra-abdominal infections, as well as for the oral treatment of gynaecological infections. However, final judgement of their position in the treatment of these diseases is not yet possible. Gatifloxacin has the highest renal excretion (about 84%) after oral administration. Therefore, it is also the most suitable for the treatment of uncomplicated and complicated UTI. The urinary excretion of moxifloxacin after oral administration is only in the range of about 20%.

TMP-SMX

The main indication for TMP alone or in combination with a sulphonamide, e.g. SMX, is the treatment of UTIs. TMP with or without SMX can also be used for the prophylaxis of recurrent cystitis. The resistance rate against E. coli can vary from country to country. Therefore, it is not recommended for empirical therapy of acute

uncomplicated cystitis or pyelonephritis, when the resistance rate in the area is > 10-20% (4). In complicated UTIs, TMP-SMX should only be used in accordance with sensitivity testing. TMR especially in combination with SMX, can lead to severe although rare adverse events, such as Lyell syndrome, Stevens-Johnson syndrome and pancytopenia.

Fosfomycin

Fosfomycin is active against Gram-negative and Gram-positive bacteria. The natrium salt is only for parenteral

use. Fosfomycin trometamol is licensed for single-dose (3 g) treatment of uncomplicated cystitis in women.

Nitrofurantoin

The antibacterial activity of nitrofurantoin is limited to the urinary tract because of its low serum concentrations. It is active against E. coli, Citrobacter and most strains of Klebsiella and Enterobacter, whereas Providencia and Serratia are mostly resistant. Proteus, P. aeruginosa and Acinetobacter are almost always resistant. It is active against Gram-positive cocci, e.g. enterococci and staphylococci. It is suitable only for the treatment or prophylaxis of uncomplicated UTIs. Short-term therapy for this indication has not been proven in sufficiently large studies. Little development of resistance has been observed over many years. Treatment can lead to severe although rare adverse events, such as chronic desquamative interstitial pneumonia with fibrosis.