Principles
of antimicrobial treatment
Antimicrobials may be used to prevent (Prophylaxis above) or treat
established wound infection. The use of antibiotics for established infection in
wounds ideally requires the isolation of the bacterium and a determination of
its sensitivity; this is the overriding first requirement, for after antibiotics
are administered, the clinical picture may be confused, the patient no better,
and the opportunity to make a precise diagnosis has been lost. However, it is
unusual to have to treat wound infections with antibiotics. Only spreading
infection or signs of systemic sepsis really justify them. Appropriate treatment
must include drainage of pus and débridement if necessary.
• the use of broad-spectrum antibiotic combinations where the organism
is not known or where it is suspected that there may be one, two or more,
usually gut-derived bacteria responsible for the infection acting in synergy.
Thus, during and following emergency surgery within the abdomen, or requiring
the opening of bowel where any of the gut organisms may be responsible for
subsequent peritoneal or bacteraemic infection, a combination of broad-spectrum
penicillin, such as ampicillin or mezbociblin with an aminoglycoside, e.g.
gentamicin, and metronidazole may be used postoperatively to support the
patient’s own body defences.
Alternatives
are a cephalosporin, e.g. cefuroxime, with metronidazole (increasingly popular
as gentamicin toxicity and monitoring of bevels are avoided), or monotherapy
using a carbapenem or quinolone.
In
surgical units with multiple resistant Pseudomonas or other Gram-negative
species (such as Klebsiella) which have become ‘resident
opportunists’, there may become a need for a rotation of antipseudornonal and
anti-Gram-negative chemotherapy between the broad-spectrum penicibbins, e.g.
azbocilbin 2 g i.v. 8-hourly and cephabosporins, e.g. ceftazidime 50—100
mg/kg per day, or cefotaxime 2 g 8-hourly.
The use of these routines, the monitoring of subsequent wound infection
and the alternation of combinations of chemotherapy should be monitored by the
infection control team. It should not be forgotten, in treating postoperative
pyrexial infection, that a failure to respond to a very broad spectrum of these
combined antibiotics requires a critical bedside review to exclude collections
of pus and other causes of a raised temperature.
New
antibiotics should be used with caution and, wherever possible, sensitivities
should have been obtained. There are certain general rules from which the choice
of antibiotics may be based originally; thus it is unusual for Pseudomonas
aeruginosa to be found as a primary infecting organism unless the patient
has had surgical or hospital treatment. Local antibiotic sensitivity patterns
vary from centre to centre and from country to country, and the sensitivity
patterns of common pathogens will be known to the hospital microbiologist.
Antibiotics
used in treatment and prophylaxis of wound infection
Antimicrobials may be produced by living organisms (antibiotics) or by
synthetic methods. Some are bactericidal, e.g. penicillins and aminoglycosides,
and others bacteriostatic, e.g. tetracycline and erythromycin. In general,
penicillins act upon the cell wall and are most effective against bacteria
that are multiplying and synthesising new cell wall materials. The
aminoglycosides act at ribosomal bevel, preventing or distorting the production
of proteins required to maintain the integrity of the enzymes in the bacterial
cell.
Penicillin.
Florey and Chain produced the first therapeutic preparation in 1941,
benzylpenicillin, which has proved most effective against Gram-positive
pathogens including most streptococci, the cbostridia and some of the
staphylococci which do not produce j3-lactamase. It is still effective against
actinomycosis, which rarely is a cause of wound infection, and may be used to
treat spreading streptococcab infections specifically, even if other antibiotics
are required as part of therapy of a mixed infection. All serious infections,
e.g. gas gangrene, require high-dose intravenous benzylpenicilbin, e.g. 1.2 g
4-hourly.
Flucloxacillin
and methicillin. These are beta-lactamaseresistant penicibbins and are therefore
of use in treating staphybococcal 3-bactamase-producing organisms. This is the
only reason for using them; and flucloxacillin has poor activity against other
pathogens.
Ampicillin
and amoxyciblin. These 3-bactam penicibbins are absorbed orally or may be given
parenterabby. Pharmacodynamically, amoxycilbin is superior. Both are effective
against enterobacteriaceae, against E. faecalis and the majority of group
D streptococci, but not species of Klebsiella or Pseudomonas.
Mezlocillin
and azlociblin. These are ureidopenicibbins with good activity against species
of Enterobacter and Klebsiella. Azlocibbin is particularly
effective against Pseudomonas. Each has some activity against Bacteroides
and enterococci, but
each is susceptible to 13-lactamase. Combined with an aminoglycoside,
mezlocibbin is a valuable treatment for severe mixed infections, particularly
Gram-negative organisms in the immunocompromised patient. Klebsiella strains
are best treated with mezlocillin, Pseudomonas strains with azlocillin.
Clavulanic
acid is available combined with amoxycibbin for oral treatment. This anti beta
lactamase protects the amoxyciblin from inactivation by beta-bactamase-producing bacteria. It is of considerable value for treating Klebsiella
strains and beta-lactamase-producing E. coli infections, but of no value
against Pseudomonas strains. Sometimes it is used for locabised
cebbubitis or superficial staphylococcal infection and should be used for
infected human and animal bites. It is available for oral or intravenous
therapy.
Cephalosporins.
There are many beta-lactamase-susceptible (not further considered here) and beta
lactamase-stabbe cephalosporins available. There are three that find a
place in surgical practice: cefuroxime, cefotaxime and ceftazidime. The first
two are most effective in intra-abdominab skin and soft tissue infections, being
active against S. aureus, and most enterobacteria. As a group, the
enterococci (S. faecalis) are not sensitive to any of the
cephalosporins. Ceftazidime, although being active against the Gram-negative
organisms and, to a lesser extent, S. aureus, is most effective against P
aeruginosa. These cephalosporins may be combined with an aminoglycoside,
such as gentamicin, or an imidazole, such as metronidazole, if guaranteed
anaerobic cover is needed.
Aminoglycosides.
Gentamicin and tobramycin have similar activity and are particularly effective
against the Gram-negative enterobacteriaceae. Gentamicin is effective against
many strains of Pseudomonas, although resistance develops rapidly, but
all aminogbycosides are inactive against anaerobes and streptococci. Serum
levels immediately before and 1 hour after intramuscular injection must be taken
48 hours after the start of therapy, and dosage should be modified such that the
trough level remains at or below 2.5 mg/litre and the peak level should not rise
above 10 mg/litre. Ototoxicity and nephrotoxicity may follow sustained high
toxic levels. They have a marked postantibiotic effect and single large doses
are effective and may be safer.
Vancomycin
is most active against Gram-positive bacteria. It is ototoxic and nephrotoxic.
Serum bevels should be monitored but this antibiotic has proved most effective
against mubtiresistant staphybococcal infection and, when given oralby, it is
effective against C. difficile in cases of pseudomembranous colitis.
Metronidazole
is the most widely used member of the imidazobe group and is active against all
anaerobic bacteria. It is particularly safe and may be administered orally (up
to 600 mg 8-hourly), rectally (up to 1 g suppository 8-hourly) or intravenously
(500 mg 8-hourly). Infections with anaerobic cocci and strains of Bacteroides
and Clostridia are effectively treated — or prevented — by its
use. Metronidazole is responsible for the reduction of anaerobic infections
after abdominal, coborectab and pelvic surgery.
Mention
has been made of meropenem which, together with imipenem, is a member of the
carbopenems, which are stable to beta-lactamase. They have useful broad-spectrum
anaerobic as webb as Gram-positive activity but are expensive.
The
quinolones are potent microbicidab agents with action against Pseudomonas spp.,
e.g. ciprofloxacin. Their clinical robe in managing wound infection has not been
defined.