Much work on the antibiotic sensitivities of numerous clostridia isolated from wounds suggested that the order of activity of the common antibiotics is, in general, tetracyclines > penicillin > chloramphenicol. Many factors must be considered in the antibiotic treatment of clostridial infections in addition to in vitro proof of antibiotic sensitivity Penicillin has been widely used and may administered with a tetracycline, but some clostridia may now be resistant to tetracycline. Metronidazole and clindamycin are very effective. The treatment of gas gangrene with penicillin and other measures has been reviewed.
Enthusiastic claims are made for the efficacy of hyperbaric oxygen therapy in gas gangrene. Patients are placed in a special pressurized chamber in which they breathe oxygen at 2-3 atmospheres pressure absolute for periods of 1-2 hours twice daily on several successive days. Hyperbaric oxygen therapy involves special equipment and, as oxygen is potentially toxic, it requires special experience and careful monitoring. Nevertheless, this form of treatment is likely to gain more widespread recognition; when it is used by experienced operators the anaerobic extension of gas gangrene may be halted and the need for major surgical intervention avoided in some cases.
PROPHYLAXIS OF GAS GANGRENE
The prevention of gas gangrene should be considered separately in relation to planned surgical wounds and to accidental wounds. In the former case, it should be recognized that Clostridium welchii is normally present in large numbers in human faeces and that its spores occur on the skin, especially in the areas of the buttocks and thighs. As clostridial spores are markedly resistant to most antimicrobial chemicals, they are likely to survive normal pre-operative skin preparation and a proportion of the spore population persists in the area of the planned incision. The numbers can be reduced by more prolonged skin preparation involving the sustained application of povidone-iodine for a day or two before operation and this procedure has a place in orthopaedic surgery. When the factors of inevitable skin contamination and likely survival of spores are combined with circumstances that predispose to devitalization of tissue and reduced oxygen tension, a patient is seriously vulnerable to the development of post-operative gas gangrene. These circumstances arise if an elderly patient or a patient with vascular insufficiency is subjected to major operative surgery involving the hip or lower limb. In such cases, there are strong arguments for insisting that penicillin should be given immediately pre-operatively (that is within a few hours) and for 5 to 7 days thereafter to guard against the possible germination and outgrowth of clostridial spores.
This principle is recognized in military circles, but delays in surgical treatment in civil practice are inevitable when major disasters such as earthquakes or large explosions occur. Prophylactic administration of benzyl penicillin (500 000 units each of potassium and procaine penicillin, repeated at intervals of six hours) in cases of serious, contaminated wounds, has largely replaced the prophylactic use of gas gangrene antisera. The use of an antibiotic in this manner must never preclude prompt and adequate wound toilet.
A polyvalent serum is available for prophylactic use and for treatment of cases in which the causal organism has not been determined. The prophylactic dose, given intramuscularly (or in urgent cases intravenously), is 10 000 international units Clostridium welchii antitoxin, 5 000 units Clostridium septicum antitoxin and 10 000 units Clostridium oedematiens antitoxin. The therapeutic dose, given intravenously, should be at least three times the prophylactic dose, and the administration should be repeated as necessary. Monovalent sera are also available for the treatment of cases after the causal organism has been identified. Reactions to antitoxin administered intravenously may be severe and precautions should be taken.
Thick, rectangular, Gram-positive bacilli suggest the presence of Clostridium welchii, Clostridium fallax. or Clostridium bifermentans; 'citron bodies' and boat or leaf-shaped pleomorphic bacilli with irregular staining may indicate Clostridium septicum; slender bacilli with round terminal spores suggest Clostridium tetani or Clostridium tetanomorphum; Clostridium oedematiens occurs in the form of large bacilli with oval subterminal spores.
Direct microscopic examination of tissue smears stained with specific antisera conjugated to different fluorescent dyes and illuminated by ultraviolet light allows prompt recognition of Clostridium oedematiens and prompt differentiation between Clostridium septicum and Clostridium chauvoei which are closely related.
In puerperal infections, and especially in cases of septic abortion, the organisms may gain access from faeces-contaminated perinea] skin to necrotic or devitalized tissues in the uterus or adnexa and set up a dangerous pelvic infection or invade the blood stream to produce intravascular haemolysis and anuria. Clostridium welchii may also be involved in infections occurring as a result of extension of the organism from the alimentary tract, as in cases of appendicitis or intestinal obstruction.
If a preparation of adrenalin used for injection is contaminated with clostridial spores, the combination of an infective focus with the local ischaemia that follows the injection may be catastrophic. Gas gangrene is well recognized as a complication of surgical operations on the lower limb or hip area of patients in whom the blood supply may be inadequate and this is discussed below.
Other less severe forms of clostridial infection may occur without the typical toxaemia, such wounds having a foul odour and showing evidence of gas formation. Moreover, potentially pathogenic anaerobes may be cultivated from a wound that never shows any signs of gas gangrene. In 1943, MacLennan classified anaerobic infections on clinical grounds and he recognizes:-
(a) Simple contamination of a wound with clostridia.
(b) Anaerobic cellulitis, in which muscle is not involved.
(c) Anaerobic: myositis, which includes clostridial gas gangrene but may also, be caused by anaerobic streptococci.
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