CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
Number 433, pp. 205–211
Host Classification Predicts Infection after Open Fracture
Thomas R. Bowen, MD; and James C. Widmaier, MD
We propose that the classification commonly used in patients
with osteomyelitis, the Gustilo classification, also is appli-
cable to patients with open fractures as a method of identi-
fying increased risk of infection because of comorbid medical
illness. The records of 174 adult patients sustaining open
fractures of long bones were retrospectively reviewed. Each
patient was sorted into Class A, B, or C based on 14 immune
system compromising factors. Class A has no compromising
factors, Class B has one or two compromising factors, and
Class C has more than three compromising factors. The as-
sociation between class and infection was examined. The in-
cidence of infection was 4%, 15%, and 30% in patients in
Classes A, B, and C, respectively. Patients in Class B were
2.86 times more likely to have an infection, and patients in
Class C were 5.72 times more likely to have an infection
when both groups of patients were compared with patients in
Class A. The Gustilo classification, location of fracture, and
tobacco use are all factors associated with infection. Patients
in Class B or C are at markedly increased risk of infection
and may benefit from additional or alternative therapies that
decrease the risk of infection.
Level of Evidence: Prognostic study, Level II-1 (retrospective
study). See the Guidelines for Authors for a complete de-
scription of levels of evidence.
Infection is a major complication in the treatment of pa-
tients with open fractures. No studies exist in the ortho-
paedic literature that classify the patient’s preinjury co-
morbid medical state with respect to the subsequent risk of
Received: June 11, 2004
Revised: August 23, 2004
Accepted: October 19, 2004
From the Department of Orthopaedic Surgery, Geisinger Medical Center,
Danville, PA.
Each author certifies that he or she has no commercial associations (eg,
consultancies, stock ownership, equity interest, patient/licensing arrange-
ments, etc) that might pose a conflict of interest in connection with the
submitted article.
Each author certifies that his institution has approved the human protocol for
this investigation and that all investigations were conducted in conformity
with ethical principles of research, and that informed consent was obtained
were deemed necessary by the authors’ institutional review board.
Correspondence to: James C. Widmaier, MD, Department of Orthopaedic
Surgery, 100 N. Academy Avenue, Danville, PA 17822. Phone: 570-271-
6541; Fax: 570-271-5872; E-mail: jcwidmaier@geisinger.edu.
DOI: 10.1097/01.blo.0000150345.51508.74
205
© 2005 Lippincott Williams & Wilkins
infection in the presence of an acute, open fracture. There-
fore, there is no objective method to identify patients who
would benefit from additional or alternative treatment to
limit the risk of infection.
The degree of soft tissue and bony disruption may best
determine the risk of infection.9 The Gustilo classification
first was developed for description of the degree of local
injury, and the association between infection and the
Gustilo classification has been confirmed.9 In addition to
the degree of soft tissue injury after an open fracture, the
anatomic location of the fracture may help determine the
risk of infection. Experimental data suggest that neutrophil
delivery to wounds of the lower extremity is reduced in
comparison to wounds of the upper extremity.15 Dellinger
et al9 reported that infection after an open fracture occurs
more frequently in the lower extremity in comparison to
the upper extremity. Therefore, there may be anatomic
variation in the inflammatory response after an open frac-
ture.
The nature of treatment also may affect the risk of
infection after an open fracture. Patzakis and Wilkins19
postulated that the timely administration of antibiotics is
the most important treatment-related factor in the preven-
tion of infection. Other factors, such as early wound cov-
erage and the number of blood transfusions also may im-
pact the risk of infection.9,14
Finally, factors relating to the patient’s general medical
health are thought to increase the risk of complications
after an open fracture. Advanced age and diabetes have
been cited,2 but the contributions of other medical condi-
tions are not defined in the orthopaedic literature.
The association between general medical health and
successful treatment of an orthopaedic infection was sup-
ported with research by Cierny et al,7 who also described
a method of classifying patients’ general medical health
when prescribing treatment for osteomyelitis. The classi-
fication, as modified by McPherson et al,17 subsequently
has been associated with outcomes in patients with infec-
tions after total joint arthroplasties. The modification of
the classification by McPherson et al17 divides patients
into three classes, A, B, or C, based on the number of
comorbid conditions that a patient has in common with a
list of 14 immune-compromising factors. Patients with no
compromising factors are in Class A. Patients in Class B

206 Bowen and Widmaier
have one or two compromising factors. Patients in Class C
have more than three compromising factors or one of the
following conditions: an absolute neutrophil count less
than 1000; a CD4 count less than 100; intravenous drug
abuse, chronic active infection of another site, or dysplasia
or a neoplasm of the immune system.
The purpose of our study was to objectively measure
the association of comorbid medical illness and subse-
quent infection after an open fracture in adult patients by
classification of the host.
MATERIALS AND METHODS
The medical records of all patients presenting to a Level I trauma
center with an acute, traumatic, open fracture of at least one long
bone between June 1, 2000 and June 1, 2003 were reviewed
retrospectively. Institutional review board approval was obtained
before initiation of the study. The following patients were ex-
cluded from the study: patients younger than 18 years; patients
with preexisting infection; patients who had penetrating trauma;
patients receiving antibiotic treatment before the injury for a
condition not related to the open fracture; patients with open
fractures of the hands, feet, spine, and pelvis without long bone
involvement; and patients with pathologic fractures. The attend-
ing surgeon and the resident on-call at the time of the patient
presented did all fracture care, including surgery. All patients
received emergent antibiotic therapy consisting of cefazolin, 1
mg intravenously every 6 hours. Gentamycin 80 mg, given in-
travenously every 8 hours, was added for patients with Gustilo
Grades II and III fractures and in patients with some Grade I
open fractures, at the surgeon’s discretion. Gentamycin dosing
was adjusted based on serum drug levels. All patients with frac-
tures occurring on a farm environment, in the presence of vas-
cular compromise, or in fractures with extensive crush injuries,
also received 3 million units of penicillin G intravenously every
4 hours. In addition to antibiotic treatment, all patients had emer-
gent operative debridement. After operative debridement, the
patient’s fracture was reclassified according to the system de-
scribed by Gustilo et al.12,13 Patients requiring one operative
procedure received at least 24 hours of antibiotic treatment, with
the majority of patients receiving 48 hours of antibiotic treat-
ment. Antibiotic treatment was extended for patients requiring
multiple procedures.
After a retrospective review of the medical records, each
patient was sorted into one of the classes described by Cierny et
al7 and modified by McPherson et al.17 Then, a fracture outcome
was noted for each open fracture. Fracture outcomes were: in-
fection; fracture union; fracture nonunion without evidence of
infection; primary amputation; death; and lost to followup. Frac-
ture union was defined as the absence of pain with weightbearing
or functional use and bony trabeculae seen crossing the fracture
site on two orthogonal views of plain radiographs. Infection was
defined as fever, erythema, wound drainage, abscess, or celluli-
tis, requiring operative treatment. Lost to followup was defined
as patients not documented as reaching an alternative study out-
come at least 90 days after presentation.
Clinical Orthopaedics
and Related Research
Factors possibly related to the incidence of wound infection
also were collected retrospectively by review of the medical
records. Specifically, the location of the fracture, the Gustilo
classification after debridement, the mechanism of injury, the
injury severity score (ISS), the patient’s age, the patient’s gen-
der, and the length of followup were recorded. The mechanism
of injury was classified as low energy, moderate energy, or high
energy. Low-energy mechanisms dissipate approximately 100
foot-pounds of energy, such as falls from a curb.5 Moderate-
energy mechanisms involve dissipation of 300–500 foot-pounds
of energy, such as skiing and bicycling injuries. High-energy
mechanisms involve greater than 2000 foot-pounds of dissipated
energy, such as automobile bumper collisions. All patients were
offered long-term followup in the orthopaedic department with-
out restriction regardless of the availability of health insurance.
Two followup dates were recorded for each patient, a followup
specifically with the treating orthopaedic surgeon and a more
general followup obtained through the study location. The study
location is a multispecialty clinic. Many patients continue to be
seen by their primary care physician or other specialists in the
clinic after discharge from orthopaedic care. Documentation of
this long-term followup in the multispecialty clinic was available
for review.
The demographics of the study population were described
using average, range, and standard deviation. Patients lost to
followup were compared with the study population using the
simple Student’s t test to identify any significant demographic
difference between the study population and those lost to fol-
lowup. A univariate statistical analysis of the patient character-
istics predictive of infection using a simple logistic regression
model was used to calculate the odds ratios, 95% confidence
intervals and p values for each patient characteristic. The asso-
ciations between common comorbidities and infection also were
examined by univariate analysis. Patient characteristics of vary-
ing levels of severity and with similar rates of infection were
grouped to simplify multivariate analysis and improve statistical
power. Then, a multivariate analysis using a multiple general
estimating equation (GEE) model was done using those groups
found in the univariate analysis to have p values of 0.20 or less.
The GEE model was chosen for multivariate analysis as it can
statistically control for multiple patients sustaining more than
one fracture.
RESULTS
One hundred seventy-four consecutive adult patients with
195 open fractures of long bones were identified as study
candidates. Twenty-eight patients (16%; 33 fractures)
were excluded from univariate and multivariate analyses
for one of the following reasons: lost to followup (21
fractures; 20 patients), primary amputation (five fractures),
death (four fractures; four patients), and insufficient docu-
mentation (three fractures; two patients). As a result, there
were 146 patients with 162 fractures included in the study.
Patients lost to followup were similar to the remaining
population with respect to all recorded demographic mea-
sures. The study population included patients with a wide
Number 433
April 2005 Infection after Open Fracture 207

range of ages, all sustaining predominantly high-energy,
blunt traumas (Table 1). Sixty-three percent of the popu-
lation had at least one medical comorbidity. The fractures
sustained varied widely in location and Gustilo classifica-
tion, except for the relatively rare Gustilo Grade IIIC in-
jury (Table 2).
The univariate analysis showed that host class, Gustilo
classification, and the location of fracture were predictive
of infection (Table 3). Age, gender, energy level of injury,
need for transfusion, ISS, time to operative treatment, and
the length of followup were not predictors of infection in
this population. Tobacco use, alcohol use, diabetes, and
malnutrition were found in more than 10 patients each,
allowing meaningful univariate statistical analysis. Of
these, tobacco use was associated with infection (p ⳱
0.02).
Following multivariate analysis, the classification de-
scribed by Cierny et al7 and Gustilo class remained pre-
dictive of infection (Table 4). In particular, a patient in
Class B was 2.86 times more likely (p ⳱ 0.007) to have an
infection when compared with a patient in Class A. Like-
wise, a patient in Class C was 2.86 times more likely (p ⳱
0.007) to have an infection when compared with a patient
in Class B. A patient with a Gustilo grade of IIIA, IIIB, or

TABLE 1. Demographic Characteristics of the Study Population

by Patient
Demographic Measurement Number
Number of patients 146
Age Mean years ± SD, (range) 47 ± 18, (18–92)
Gender Males (%) 96 (66%)
Number of 1 open fracture (%) 130 (89%)
fractures
2 open fractures (%) 16 (11%)
Mechanism MVA (%) 70 (48%)
MCA (%) 14 (10%)
Fall (%) 27 (18%)
Industrial (%) 15 (10%)
Pedestrian versus car (%) 10 (%)
Other (%) 10 (%)
Energy level Low (%) 17 (12%)
Moderate (%) 16 (11%)
High (%) 113 (77%)
Host class A (%) 54 (37%)
B (%) 78 (53%)
C (%) 14 (10%)
Injury Severity Mean ± SD, (range) 16 ± 11 (4–50)
Score
Comorbidities Age > 79 years (%) 7 (5%)
Tobacco (%) 57 (39%)
Alcohol (%) 35 (24%)
Diabetes (%) 13 (9%)
Malnutrition, albumen ⱕ 3.0 17 (12%)
g/dL (%)
Systemic inflammatory disease (%) 2 (1%)
Immunosuppressive drugs (%) 3 (2%)
Pulmonary insufficiency (%) 4 (3%)
Malignancy (%) 4 (3%)
Hepatic insufficiency (%) 2 (1%)
Chronic active dermatitis (%) 2 (1%)
Intravenous drug abuse (%) 3 (2%)
Renal failure (%) 1 (1%)
Time to operating Mean hours (SD, range) 5.6 (7.2), (0.8–59.8)
room
Transfusions Mean number (SD, range) 4.6 (7.6), (0–53)
Followup PCP, mean days (SD, range) 486 (312), (97–1374)
Orthopaedics, mean days (SD, 354 (260), (97–1374)
range)

PCP = primary care provider; MVA = motor vehicle accident; MCA = motorcycle accident
 Clinical Orthopaedics
208 Bowen and Widmaier and Related Research

TABLE 2. Demographic Characteristics of the entirely predictive of infection, suggesting that factors dis-
Patients by Fracture tant to the fracture site also may influence the risk of
Fracture Classification Number infection. Dellinger et al9 found that infection was ap-
proximately three times more common in the leg than the
Number of fractures 162
arm. Basic science research has confirmed delayed neu-
Gustilo classification I (%) 44 (27%)
II (%) 67 (41%) trophil delivery to wounds of the lower extremity in com-
IIIA (%) 22 (14%) parison to wounds of the upper extremity, suggesting an
IIIB (%) 24 (15%) anatomic variation in the inflammatory response.15 There-
IIIC (%) 5 (3%) fore, the anatomic location of the fracture also may influ-
Location Upper arm (%) 11 (7%)
ence the risk of infection.
Forearm (%) 40 (25%)
Thigh (%) 34 (21%) Factors related to treatment also may affect risk of in-
Leg (%) 77 (48%) fection. Patzakis et al18,19 postulated that the timely ad-
Outcome Healed (%) 127 (78%) ministration of antibiotics is the most important factor re-
Nonunion (%) 15 (9%) lated to treatment in the prevention of infection. Harley et
Infected (%) 20 (12%)
al14 subsequently confirmed these findings. Delayed
wound coverage also is likely linked to infection, specifi-
cally secondary to nosocomial organisms.6,8,10,11 Finally,
blood transfusion may have an immunosuppressive effect
IIIC was 7.85 times more likely (p ⳱ 0.001) to have and may be associated with an increased risk of infection.9
infection when compared with a patient with a Gustilo Factors relating to the patient’s general health, namely
Grade I or Grade II fracture. Fracture location was not advanced age and diabetes mellitus, also are thought to
statistically significant in this population but was retained increase the risk of infection.2 For example, the increased
in the regression model because the p value was less than rate of infection after fractures of the ankle in patients with
0.10 and the odds ratio was relatively large. diabetes is established in the orthopaedic literature.3 The
cause of the increased rate of infection in patients with
DISCUSSION diabetes who sustain ankle fractures is likely multifactorial
and includes relative immunosuppression, vasculopathy,
Historically, death from sepsis after an open fracture was neuropathy, and possibly anatomic location. Moreover, the
commonplace, and the treatment of open fractures of the exact contribution of many medical conditions more rare
long bones with amputation remained standard care well than increased age or diabetes is not known. Dellinger et
into the 19th century. The modern concept of debridement al9 explicitly excluded patients with “chronic health prob-
with removal of all foreign material and open wound man- lems, such as diabetes, peripheral vascular disease or ste-
agement, rather than amputation, did not gain full accep- roid use” in their series of patients with open fractures.
tance until the end of World War I.2 Other improvements Similarly, the LEAP study excluded patients older than 69
in surgical care, such as asepsis, anesthesia, fluid resusci- years and patients with a documented psychiatric disorder
tation, and early fracture stabilization have made primary or mental retardation.16 Therefore, the current orthopaedic
amputation unnecessary in many situations. Nonetheless, trauma literature may be under representing the effect of
infection remains a major hurdle in limb salvage, compli- the patient’s general medical health by reporting recon-
cating as much as 50% of all cases in selected popula- struction results on a subset of relatively healthy patients.
tions.9 The importance of the patient’s general medical health
Multiple factors are known to affect the incidence of in the treatment of established orthopaedic infection has
infection after open fracture, with the severity of the local been described. Cierny et al7 first classified patients’
soft tissue injury being most influential. Many open frac- medical health, and used the class system to determine the
ture classification systems describing the soft tissue injury best treatment for patients with osteomyelitis. The class
correlate with the risk of infection. The Gustilo classifica- system was so strongly predictive of outcome in the treat-
tion has had the most widespread popularity, and the as- ment of osteomyelitis that Cierny et al recommended pal-
sociation between the Gustilo classification and the risk of liation, rather than surgical treatment for many patients in
infection is established.9 However, the sensitivity of the Class C.7 The class system was modified by McPherson et
Gustilo classification becomes limited as fractures become al17 and applied to the treatment of patients with infected
more severe.2 Gustilo et al13 improved the classification total hip prostheses. McPherson et al17 showed that a
by adding the subgroups IIIA, IIIB, and IIIC to address the higher class was associated with increased failure of treat-
need for increased sensitivity in Grade III fractures. De- ment. Therefore, the class may be one method to estimate
spite the improvements, the Gustilo classification is not the patient’s ability to mount a successful immunologic
Number 433
April 2005 Infection after Open Fracture 209

TABLE 3. Results of the Univarite Analysis of Predictors of Infection

Variable Infection No Infection OR 95% CI p Value
Number of patients 20 142
Age Mean (SD) 46 (17) 47 (18) 0.96* 0.74–1.26 0.78
Gender Male (%) 17 (16%) 91 (84%) 3.18 0.89–11.36 0.076
Female (%) 3 (6%) 51 (94%)
Energy Low or moderate (%) 1 (3%) 33 (97%) 5.75 0.74–44.60 0.094
High (%) 19 (15%) 109 (85%)
Class A (%) 2 (4%) 55 (96%) 3.38 1.51–7.56 0.003
B (%) 13 (15%) 76 (85%)
C (%) 5 (31%) 11 (69%)
Injury Severity Score Mean (SD) 15.6 (9.1) 16.0 (10.7) 0.97* 0.61–1.53 0.89
Tobacco use Yes (%) 13 (20%) 52 (80%) 3.21 1.21–8.57 0.020
No (%) 7 (7%) 90 (93%)
Alcohol use (%) Yes (%) 7 (19%) 30 (81%) 2.01 0.74–5.48 0.17
No (%) 13 (10%) 112 (90%)
Diabetes Yes (%) 2 (13%) 15 (87%) 1.10 0.23–5.29 0.90
No (%) 18 (12%) 129 (88%)
Malnutrition Yes (%) 5 (23%) 17 (77%) 2.45 0.79–7.60 0.12
No (%) 15 (11%) 125 (89%)
Time to surgery Mean (SD) 5.2 (7.5) 3.9 (2.0) 0.62* 0.19–2.07 0.44
Transfusion Yes (%) 15 (16%) 77 (84%) 2.53 0.87–7.34 0.087
No (%) 5 (7%) 65 (93%)
Gustilo classification I or II (%) 5 (5%) 106 (95%) 8.83 3.00–26.02 < 0.001
IIIA, IIIB, or IIIC (%) 15 (29%) 36 (71%)
Location Leg 15 (19%) 62 (81%) 3.87 1.33–11.23 0.013
Thigh, forearm, or upper arm 5 (6%) 80 (94%)

*OR = odds ratio; corresponds to a 10-unit increase in age, Injury Severity Score, and time to operating room, respectively; CI = confidence interval

response in the face of any orthopaedic infectious chal-
lenge, including an acute, open fracture.
Results of our study support the hypothesis that de-
creased general medical health is associated with an in-
creased risk of infection after an open fracture. In this
series, the effect of poor health is profound and second
only to the Gustilo classification in association with infec-
tion. Also, poor health is common in the patients, with
63% of the population in Class B or C. Nevertheless, the
overall incidence of infection of 12% is comparable with
the incidences in similar series (Table 5).9,14,18 The step-
wise progression of the odds ratio and incidence of infec-
tion between Class A and Class B, and Class B and Class
C, simplifies the clinical application of the classification
(Fig 1). The association between tobacco use and infection
is consistent with previous reports of generally increased
fracture complications in subjects who smoke.1,20,21 How-
ever, the lack of statistical significance between anatomic
location and infection on multivariate analysis is contrary
to other published series and is most likely attributable to
insufficient statistical power. Also, the incidence of poor
medical health in our patients was high, and its effect may
have masked other determinants of infection such as ana-
tomic location. The lack of association between the num-
ber of blood transfusions and infection may be attributable
to insufficient power or inconsistency in the use of blood
products in this series of patients. Conversely, the lack of
association between diabetes and infection cannot be ex-

TABLE 4. Results of Multivariate Analysis of Independent Predictors of Infection Using the Multiple GEE
Regression Model
Variable Estimate SE OR 95% CI p Value
Intercept −4.51 0.75 – – –
One level increase in host class 1.05 0.39 2.86 1.33–6.18 0.007
Gustilo Class IIIA, IIIB, IIIC versus Class I or II 2.06 0.60 7.85 2.41–25.59 0.001
Location of leg versus thigh, forearm, or upper arm 0.96 0.58 2.61 0.85–8.09 0.095

GEE = general estimating equation; CI = confidence interval; OR = odds ratio; SE = standard error
 Clinical Orthopaedics
210 Bowen and Widmaier and Related Research

TABLE 5. Incidence of Infection after factors relating to the Gustilo classification is problematic.
Open Fracture This interobserver variability may explain the similar rates
Study Total Grade I Grade II Grade III of infection in Gustilo Grades I and II or IIIA, IIIB, and
IIIC fractures in this study. Also, the medical status of the
Dellinger et al9 16% 7% 11% 32%
Harley et al14 11% 2% 6% 22%
patients treated in our study was not central to their emer-
Patzakis et al18 7% 1.4% 3.6% 22.7% gent care. Relatively stable medical comorbidities, such as
Current study 12% 7% 3% 27% tobacco use or borderline protein malnutrition may be un-
derreported in the medical records. Conversely, borderline
malnutrition may be overreported, as aggressive fluid re-
suscitation can spuriously suppress blood albumen con-
plained by insufficient power. Diabetes may not be di- centrations. Finally, the treating orthopaedic surgeon was
rectly associated with an increased risk of infection in this not blinded to the patient’s comorbid medical conditions
series of patients. Rather, at the ankle, conditions com- and may have been influenced to choose alternative treat-
monly associated with diabetes, such as peripheral vascu- ment methods with a presumably lower risk of infection.
lar disease and neuropathy may be to blame. Alternatively, For example, a surgeon may choose to accept a larger
simply the diagnosis of diabetes may be insufficient to amount of acute limb shortening to avoid free tissue trans-
increase the risk of infection in this population, and a more fer in a medically ill patient with an open fracture.
sensitive measure, such as HbA1c, may be more predictive We used a previously established classification to mea-
of infection. The time to operative treatment was not as- sure the association between comorbid medical illness and
sociated with an increased incidence of infection in this the development of infection after an acute, open fracture.
series. This finding is also consistent with other series In this patient population, the classification by Cierny et
suggesting that the timing of operative debridement is less
al7 was prognostic for the risk of infection. We recom-
critical in the presence of emergent intravenous antibiot-
mend that surgeons consider additional or alternative
ics, fluid resuscitation, and local wound care.14,18,19 Also,
therapies to limit the risk of infection in patients in Classes
in our study the average time to operative debridement was
B and C. Hopefully, by using this class system the surgeon
relatively small. Therefore, the majority of patients may
can better predict the potential risk of an infection after an
have had operative debridement before a critical threshold
open fracture before treatment.
was attained.
The major weakness of this study is its retrospective
design. The Gustilo classification best determines risk of Acknowledgment
infection in patients in this study. However, the Gustilo
We thank Mr. G. Craig Wood, Biostatistician for the Weis Cen-
classification has been shown to have poor interobserver ter for Research, for valuable assistance.
reliability.4 Therefore, comparison among patients, treated
by different surgeons without a uniform method of docu-
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