It might appear somewhat provocative to raise the question of antibiotics in the treatment of an open fracture, particularly if we refer to current practice. The prescription of antibiotics is in fact the rule, probably based more on habit than on clearly known facts.
Infectious complications, a threat for all open fractures, mobilise surgeons' attention, but indi- vidual situations are complex; the situations are as different as the fracture sites, the degree of se- verity of damage to the soft tissue, the underlying host conditions, and the levels of contamination of the wounds.
Today, stabilisation of the fractures by osteo- synthesis is the rule. Whatever fixation used, it will increase the risk of infection. Careful debridement, cleaning of the wounds, immediate or secondary closing of the wounds and antibiotic treatment are the methods of treatment traditionally used to reduce the risk of infection. In this approach, the question of the effectiveness of antibiotic treatment is therefore worth asking. But in view of the com- plexities of open fractures, in order to try to answer it, we need to reformulate the question by selecting three fields of investigation: the overall effective- ness of antibiotics, assessing their effectiveness ac- cording to the type of open fracture, and finally the correlation of their effectiveness and the way the antibiotics are administered, that is the choice of molecule, time when the treatment is started and the length of administration.
Is It Any Use Prescribing Antibiotics to Reduce the Number of Infections After an Open Fracture?
Before examining the clinical work that would en- able us to answer this question, it is worth look- ing at Worlock's experimental model [1]. In this model of an open fracture of the tibia in the rab- bit, the osteosynthesis is carried out by an intra- medullary pin, and the wound is inoculated with staphylococcus. The effect of a single injection of
cefradine is maximally effective when it takes place before the bacteria are inoculated. This cor- roborates the work of Burke [2], which lays down the foundations of surgical antibiotic prophylaxis for planned surgery. The remainder of the study, on the other hand, covers the real situation of open fractures: the administration of antibiotics only after bacterial inoculation. In these experi- mental conditions, the effect of this same single dose of antibiotics is more limited, but still per- sists, decreasing by the order of 40% the infection rate as compared with the control animals.
In the clinical situation with human beings, a placebo effect is required to demonstrate the ef- fectiveness of antibiotic treatment. Three studies of this type are available.
Patzakis [3] compared three groups of patients presenting an open fracture: one group without antibiotics; one group treated with the combina- tion penicillin/streptomycin for 10 days, and one group treated with cefalotine for 10 days. The rates of infection were respectively 13.9, 9.7 and 2.3%. The effectiveness of treatment with antibiot- ics seems to be proven but is only spectacular when dealing with an antistaphylococcal antibio- tic.The study was not carried out in double-blind conditions, nor was it possible in each group to classify the fractures by type, so that we do not know whether each of the groups includes the same proportion of fractures with high risk of in- fection (grade III).
In Bergman's study [4], 90 open fractures were randomised in three groups treated with dicloxa- cillin, benzylpenicillin or placebo. No infection occurred after grade I fractures in any of the groups. With regard to grade II and grade III fractures, 12 patients were treated with dicloxacil- lin, 10 with penicillin, and 13 with placebo. Two deep infections were observed in the placebo group, and none in the treated groups.
Finally, Braun [5], in a randomised prospective double-blind study comparing placebo and cloxa- cillin, showed a higher significant reduction of in-
Rationale for Antibiotic Prophylaxis in Open Fractures
J. Gaudias
fection rates in the cloxacillin group (2/50 as compared to 12/50 in the placebo group). The fact that there were more grade III fractures in the antibiotic group if anything reinforces this result.
These three studies carried out against placebo give us a first positive answer to the question of the effectiveness of antibiotics in cases of open fracture, at least as an across-the-board response.
The Effectiveness of Antibiotics Depends on the Kind of Open Fracture
Several classifications of increasing complexity have been established to characterise open frac- tures more precisely. The classification of Gustilo and Anderson [6] seems to be the most widely used; this is in fact the only classification that has been correlated with the risk of infection. In a prospective study covering 240 patients treated for open fracture of the limbs, Dellinger [7] was able to determine the risk of infection from these fractures, by stratifying them on the basis of the Gustilo classification. In a multivariate analysis, three factors appear to be significantly correlated with the risk of infection: in the order of increas- ing importance they are the grade of the fracture (p<0.001), the use of internal or external fixation (p<0.005), and its location on the tibia (p<0.01).
The risk of infection increases with the gravity of the lesions to the soft tissue. The grade I frac- tures have a relative risk of 1, the grade II frac- tures 1.3, and grade IIIA fractures 2.1. Grades IIIB and IIIC are identical and their correlative risk is 23. The increase in the risk of infection when fractures move from grade IIIA to grade IIIB or C is 15 times greater than in the transition from grade I to II or grade II to grade IIIA. In this study, the use of antibiotics was the same what- ever the gravity of the lesions of the soft tissue.
By definition this transition from grade IIIA to grades IIIB and IIIC indicates a degree of lesions to the soft tissue beyond which it is impossible to obtain cover for the bone structure, as well as an effective means of local defence of the host, and in vivo effectiveness of the antibiotics. In this sit- uation it is possible that the preventive action of the antibiotics may be insignificant in grade IIIB and IIIC fractures.
Methods of Administering Antibiotics in Cases of Open Fracture
Before dealing with the question of the choice of molecule, it is worth raising the question of the
usefulness of taking bacteriological samples as a possible guide for secondary adaptation of the antibiotic treatment. If there is any received wis- dom in this matter, it is a priori that of original contamination of the wound as the origin of the risk of infection. Let us leave aside the special and very rare situation of heavy groundwater con- tamination, which might occur with certain wounds, for example in an agricultural environ- ment. In the usual traumatological situation, in countries that have developed effective systems for emergency care, open fractures are immobil- ised at the accident site, and the wounds are dis- infected and covered with sterile dressings. Long- standing data report 70% initial contamination [8, 9]. More recently, the bacteriological analysis of the wounds on admission to hospital shows a low rate of contamination of these wounds of the order of 30% [10, 11]. The isolated bacteria are mainly those from the skin environment. When infection occurs, the infecting bacteria are as a rule different from the initially contaminating bacteria and the infection comes, in most cases, from hospital bacteria. The proportion of infec- tion with negative gram and with relatively resis- tant bacteria increases with the severity of the lesions of the soft tissue. At the stage of the onset of the infection, this disappearance of the initial contaminating bacteria is a sign of the effective- ness of the initial surgical measures such as de- bridement and cleaning of the wounds. The fact that the infecting bacteria are hospital bacteria leads us to reflect on the strict compliance with and tightening of the traditional rules of hospital hygiene, which may have been unconsciously ne- glected in these so-called ªemergencyº situations.
Choice of the Ideal Antibiotic
The older studies mentioned initially advocated the use of an active molecule to deal with the sta- phylococci. Randomised prospective clinical trials comparing the molecules with one another are relatively rare.
Vasinius [12], in a comparative study covering 227 patients, compared the effectiveness of clinda- mycin to that of cloxacillin. The overall rate of in- fection was 15%. In the fractures treated with clindamycin, infection occurred in 9.3% of cases, as compared to 20% in the group treated with cloxacillin. The effectiveness of the antibiotics was only obvious in the fractures of grade I and II, while the fractures of grade III indicated high rates of infection of 70%, with 45% infection with
negative gram bacillus not covered by the spec- trum of the two chosen antibiotics.
Gagey [10] and collaborators compared pro- spectively and randomly the effectiveness of one single dose of 800 mg of pefloxacin and one intra- venous treatment with cefazolin for 48 h followed by oxacillin administered orally for 72 h. The groups comprised 300 patients per group and in- cluded essentially grade II fractures. Twenty-one infections were described in the group treated with pefloxacin (6.6%), 24 in the cefazolin±oxacil- lin group (8%); the difference between the two groups was not significant.
Patzakis [13], in a randomised prospective double-blind study, recently compared monother- apy using ciprofloxacin with an associated treat- ment using cefamandole and gentamicin. The rate of infection for grade I and grade II fractures was 5.8% in the ciprofloxacin group and 6% in the ce- famandole±gentamicin group, with no significant statistical difference. The data changed radically for grade III infections: the rate of infection was 31% in the ciprofloxacin group and 7.7% in the cefamandole±gentamicin group. In the study in question, the difference was not statistically sig- nificant in view of the low numbers in each group, although the risk of infection was five times higher in the ciprofloxacin group.
Timing and Length
of Antibiotic Administration
This data have been studied very little in the lit- erature. The older studies [3±5] mostly refer to 10 days of treatment; the latest development in the literature would favour a shorter treatment. Ga- gey, using a single dose of pefloxacin, obtained equivalent results to those found in longer treat- ments [10].
Dellinger [7], in his prospective study concern- ing the risks of infection, evaluated in parallel two aspects of antibiotic treatment: first, that of the moment of administration in relation to the moment when the fracture occurred and second, the length of administration.
Concerning the first point, no difference ap- pears as regards the risk of infection between the group of patients who had benefited from the ad- ministration of antibiotics in the first 3 h follow- ing the lesion and those treated more than 3 h after the fracture.
On the second point, the prospective study di- vided the group up into four categories according to the length of administration of the antibiotics (cefamandole or cefazolin): the shortest treatment
consisted of two doses of the antibiotic adminis- tered at an 8-h interval; the other groups of pa- tients were treated respectively for 1, 3 and 5 days. The effectiveness of the treatment with anti- biotics was the same in this study, whatever the length of administration of the antibiotic.
Practical Conclusion
As things now stand with regard to objective data from the medical literature, it is possible to note the following facts:
· The controlled use of antibiotics is useful in re- ducing the risk of overall infection after open fracture. This measure is in addition to, but in no case is a replacement of, surgical debride- ment and debridement of the wounds.
· This beneficial use of antibiotic treatment very likely concerns only fractures of grades I, II and IIIA using the Gustilo and Anderson clas- sification.
· In all cases the antibiotic chosen must have a high rate of effectiveness against staphylococ- cus. No molecule in the literature has shown greater effectiveness than the others, as long as this criterion is respected.
· A brief administration of antibiotics for 24±
48 h is a priori largely sufficient to obtain the optimal effect of the chosen antibiotic while curbing the risk of secondary effects and the pressure of selection.
· Finally, it is crucial to remind all those taking charge of open fractures that the bacteriologi- cal data that are obtained once the infection occurs often indicate bacteria of hospital origin and therefore the nosocomial nature of these infections.
These different propositions apply particularly to fractures of grades I, II and IIIA Gustilo classifi- cation fractures, which all enable the wound at the fracture site to be closed or at least to be cov- ered by living tissue and properly vascularised.
The prognosis for IIIB and IIIC fractures still re- mains worrying as far as infection is concerned and always raises the question of the optimal treatment. Logically, for grade IIIC fractures, the only prospect for improvement is by shortening the treatment times by removing the ischaemia as early as possible through vascular repair. For grade IIIB fractures, the reduction of the risk of infection is probably far better dealt with in the discussion about the rapid closing of the skin by reconstructing the soft tissue. A few teams have provided reconstructions at the same time, offer-
ing attractive prospects in the field of infection [14±16], but these are very short series, and aimed at selected patients, excluding all patients who presented an earlier arteriopathy of any kind or poor host conditions. The practices most used are those of a two-stage treatment, in which the reconstruction of the soft tissue needs to be car- ried out as soon as possible after the initial de- bridement phase. In this particular situation, the question of antibiotic treatment arises at the dif- ferent stages of the operative procedure. If pro- phylactic antibiotic monotreatment is the rule for fractures of grades I, II, and IIIA, the recent work of Patzakis [13] shows for the first time the inter- est of an association of antibiotics widening the spectrum in the treatment of high-grade frac- tures. We must, however, recall that the grade of the fracture can only be confirmed after surgical debridement, which means that widening the spectrum can only be considered at a secondary stage. It is sensible and logical to offer monother- apy using an antistaphylococcal antibiotic, whose effectiveness has been proven across the board to all patients, at least for the first dose.
This being the case, several attitudes could the- oretically be discussed:
· Association of antibiotics widening the spec- trum, continued until the stage of reconstruc- tion of the soft tissue; possible adaptation of treatment depending on bacteriological sam- pling carried out during the reconstruction period.
· Short initial antibiotherapy, then resuming wide-spectrum prophylactic treatment, also briefly, during the reconstruction phase, with or without adaptation to the results of the bac- teriological sampling results.
· Systemic antibiotic treatment and management of the waiting period before reconstruction of the soft tissue by local antibiotic treatment.
The use of gentamicin cement beads in sur- face application on losses of substance was tested in particular by Moehring, with good results [16].
In all these different examples, the different approaches raise the question of the optimal length of antibiotic treatment, whether continuous or sequential, local or general. No response has been found in the literature and the question still remains to be answered. Since the relatively rare occurrence of high-grade fractures leads each team to offer its own rationale in administering antibiotics, it is rather unlikely that a consensus will emerge in the short term concerning the right attitude for this kind of fracture.
The simplest propositions for the use of antibi- otics after open fracture consist in very brief treatment with an active antistaphylococcal agent for all open fractures, administering the first dose as soon as possible. The use of the Gustilo/Ander- son classification, the only one to have been cor- related with the risk of infection, makes it possi- ble on leaving the operating theatre to identify the fractures for which the risk of infection is particularly high (grade IIIB±IIIC). It is likely that for these fractures the prevention of the infection is essentially in the hands of the surgical team, relying on the quality of the debridement and the possibilities of rapid reconstruction of the soft tissue and of wound closure. To our today's knowledge, the widening of the scope of antibiotic treatment is left to the team's discretion. No fac- tors indicating advantages in prolonging treat- ment beyond the few days following the achieve- ment of wound closure at the operation site have been found.
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