basic quinolone structure dramatically increased the antibacter-
ial potency of the more modern quinolones, particularly against
Pseudomonas. Oral bioavailability is good and thus the 4-fluoro-
quinolones offer an oral alternative to parenteral aminoglyco-
sides and antipseudomonal penicillins for treatment of
Pseudomonasurinary and chest infections. Although the 4-fluo-
roquinolones have a very broad spectrum of activity, all of those
currently available have very limited activity against strepto-
cocci. Most experience has been obtained with ciprofloxacin,
which has the additional advantage of being available for intra-
venous use. The quinolones inhibit bacterial DNA gyrase.
Uses
Ciprofloxacinis used for respiratory (but not pneumococcal),
urinary, gastro-intestinal and genital infections, septicaemia
and meningococcal meningitis contacts. In addition to
Pseudomonas, it is particularly active against infection with
Salmonella,Shigella,Campylobacter,NeisseriaandChlamydia. It
is ineffective in most anaerobic infections. The licensed indica-
tions for the other quinolones are more limited. Ciprofloxacin
is generally well tolerated, but should be avoided by epilep-
tics (it rarely causes convulsions), children (it causes arthritis in
growing animals) and individuals with glucose-6-phosphate
dehydrogenase deficiency. Anaphylaxis, nephritis, vasculitis,
dizziness, hepatic and renal damage have all been reported.
An excessively alkaline urine and dehydration can cause uri-
nary crystallization.
Pharmacokinetics
Approximately 80% of an oral dose of ciprofloxacinis system-
ically available. It is widely distributed entering all body com-
partments including the eye and the CSF. Ciprofloxacinis
removed primarily by glomerular filtration and tubular secre-
tion. The half-life is four hours.
Drug interactions
Co-administration of ciprofloxacinandtheophyllinecauses
elevated blood theophyllineconcentrations due to inhibition
of cytochrome P450. As both drugs are epileptogenic, this
interaction is particularly significant.
RECENTLY INTRODUCED ANTIBACTERIAL
AGENTSIncreasing antibiotic resistance (especially meticillin-resistant
Staphylococcus aureus(MRSA) and vancomycin-resistant ente-
rococci) is a matter of deep concern. Although the spread of
multi-resistant organisms can be minimized by judicious use
of antibiotics and the instigation of tight infection-control
measures, there is a continuing need for the development of
well-tolerated, easily administered, broad-spectrum anti-
biotics. Table 43.2 lists some recently introduced antibiotics
which fulfil these criteria, together with their main features.
At present, their use is restricted and should be administered
under close microbiological supervision.
COMMONLYPRESCRIBEDANTIBACTERIALDRUGS 331Key points- If practicable, take specimens for microbiological
analyses before starting antibacterial therapy. - Consider the severity of the illness.
- Consider the likely pathogen(s).
- Consider patient factors, particularly allergies and
potential drug interactions (see text). - Select the most appropriate route of administration.
- Monitor the response and alter the therapy and route
of administration as appropriate. - Some drugs require routine plasma concentration
monitoring (e.g. aminoglycosides, vancomycin). - For most bacterial infections other than those involving
bone, joint or heart valve tissue, five to seven days of
treatment are sufficient.
Case history
While on holiday in Spain, a 66-year-old man develops a
cough, fever and breathlessness at rest. He is told that his
chest x-ray confirms that he has pneumonia. He is started on
a seven-day course of oral antibiotics by a local physician and
stays in his hotel for the remainder of his ten-day holiday.
When he returns home, he is reviewed by his own GP who
notices that he looks pale and sallow and is still breathless on
exertion, but his chest examination no longer reveals any
signs of pneumonia. A full blood count reveals a haemoglo-
bin level of 6.7 g/dL (previously normal), normal white blood
count and platelets, and a reticulocyte count of 4.1%.
Question
What other tests should you do and what antibiotics would
be most likely to cause this clinical scenario?
Answer
The patient received a course of antibiotics for pneumonia
and then developed what appears to be a haemolytic
anaemia. This could be further confirmed by raised uncon-
jugated bilirubin levels and low haptoglobin levels, and
observation of target cells and poikilocytosis on the blood
film.Mycoplasmapneumonia should be excluded by per-
formingMycoplasmatitres, as this can itself be complicated
by a haemolytic anaemia.
However, considering the drugs as the potential cause, it is
important to define the patient’s glucose-6-phosphate dehy-
drogenase status, and if he was deficient then to consider such
agents as co-trimoxazole (containing sulfamethoxazole, a
sulphonamide), the fluoroquinolones (e.g. ciprofloxacin
or nitrofurantoin) or chloramphenicol, which can cause
haemolytic anaemia in susceptible individuals. Note that chlo-
ramphenicol is more commonly prescribed in certain countries
on the European mainland. Aplastic anaemia (not the picture
in this patient) is a major concern with the use of systemic
chloramphenicol. If the patient’s glucose-6-phosphate dehy-
drogenase status is normal, then rarely the β-lactams (peni-
cillins or early (first- and second-) generation cephalosporins)
or (less likely) rifampicin may cause an autoimmune
haemolytic anaemia due to the production of antibodies to
the antibiotic which binds to the red blood cells. This could be
further confirmed by performing a direct Coombs’ test in
which the patient’s serum in the presence of red cells and the
drug would cause red cell lysis. Management involves stop-
ping the drug, giving folic acid and monitoring recovery of the
haemoglobin. It should be noted in the patient’s record that
certain antibiotics led him to have a haemolytic anaemia.