ANTIBIOTICS IN CLINICAL PRACTICE

The Clinical Use of Antibiotics : Hillas Smith

Antibiotic Therapy--Laboratory Techniques : C, T. Keane

Side Reactions to Antibiotics : A. I. Scott

THE CLINICAL USE OF ANTIBIOTICS

Hillas Smith

The Royal Free Hospital, London.

H toR. thank
President, Professor Gatenby, ladies and gentlemen, I would first like
you for inviting me to speak at your annual, "Growing Points in
Medicine" Symposium. I must say what a great pleasure it gives me to
b~ here in my native Dublin.
My topic today is the clinical use of antibiotics--more correctly antimic-
robial chemotherapy, and I intend to interpret the clinical implication of the
title rather literally, perhaps to the detriment of the scientific aspects of
chemotherapy. The contemporary era in chemotherapy begins with the dis-
covery of prontosil in the 1930s by Domagk. The active principle proved to
be para-aminobenze sulphonamide and subsequently a large number of sul-
phonamide compounds came into clinical use. A number of these are still
with us. However, even b~fore Domagk's discovery Fleming in 1929 made
his original observations on the lytic phenomenon caused when his staphy-
lococcal colonies were contaminated by a mould, the so called "Praed Street
mould". However, penicillin was not introduced until about 1940.
In the 1940s therefore the clinician wishing to treat bacterial infection
could choose between sulphonamide, penicillin or a combination of these
compounds, but the following decades saw the introduction of very many
other compounds--streptomycin, the tetracyclines, chloramphenicol, cepha-
Iosporins and many others. Today one of our problems therefore is that of
selection, that is to say we have an opportunity of choosing a drug or com-
bination of drugs which we hope will be most effective and least toxic in the
treatment of a particular patient. The clinician is faced with a bewildering
array of compounds provided by the combined skills of the soil microbiolo-
gists, organic chemists and the pharmaceutical industry. He must not be
overawed by the opportunities of choice: some knowledge of at least a
limited range of drugs in regard to antimicrobial spectrum, pharmacology
and side effects is obligatory.
Even before one reaches the stage of choosing a drug one is confronted
with the other major requirements in acute infections--diagnosis--and for
practical purposes I will deal with septicaemia only, which we may look on
as a prototype for any acute infection. Diagnosis in this context must mean
clinical diagnosis, for if we are to get the best from available drugs therapy
6 IRISH JOURNAL OF MEDICALSCIENCE---SUPPLEMENT.JUNE 1975

in the majority of acute cases and particularly in septicaemia, diagnosis will

be required long before full bacteriological assessment can be completed.
I would like to stress therefore that clinical diagnosis at the bedside is of
paramount importance. Continuing with the example of septicaemia I be-
lieve it can be shown that this diagnostic process can be managed in three
separate steps.

1. Does the patient have an infection ?

it is important to realise that very many conditions may present acutely
with fever and are unrelated to infection. Examples include primary neo-
plasms, particularly carcinoma of the kidney, carcinoma of the stomach, and
disseminated carcinoma usually with multiple liver metastases. Lymphoma,
Hodgkin's disease and leukaemia may also present with fever. The other
major groups in this category include collagen diseases, thrombotic epi-
sodes, hypersensitivity states and allergy. Factitious fever must be remem-
bered. Before moving on to the second step in diagnosis one should em-
phasise that the main pitfall here is in equating fever with infection. If we
can conclude that infection is present (and at this stage one may have white
cell count, Gram stained smear of body fluids and plain x-rays to help) we
may move to the second step.

2. What kind of infection ?

Here one must think of lists of possible pathogens, such as fungi, pro-
tozoa, mycoplasmas, leptospires, viruses and bacteria. It is important of
course to have some knowledge of the way in which these various patho-
gens are capable of producing disease and one must be familiar with the
evolution of typical infections produced by common pathogens. It should
be stressed that today very many infections may not produce a typical or
Classical picture because of prior antibiotic therapy. It is useful to know
what drugs have been used and why they may have failed. If then one is
able to select a pathogen, and for the present exercise this really means
choosing a bacterial cause, we must pass on to the third step, which is : - -

3. What bacteria ?
I do not say that one can always make an aetiological diagnosis at the
bedside, but there are sufficiently well developed patterns in many infec-
tions and taken together with certain clues one will often be able to make a
nice guess at the most likely bacterial pathogen. Even if one can decide
between, say, Gram-positive and Gram-negative organisms, then one will
have at least some basis for selecting initial therapy.
What I have said so far is that with some knowledge of the available drugs
and with an interest in thinking in microbial terms rather than in anatomical
diagnoses one can frequently select appropriate therapy for individual
patients. Perhaps in the past we have stressed too much the importance of
anatomical or organ-related diagnosis. For effective chemotherapy we must
learn and train our students to think microbially.

Taking specimens
It must be emphasised again that samples for examination should be
taken before therapy is started and this applies particularly to blood cultures