Stephen L. Henry

Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases

We reviewed 1085 consecutive compound limb fractures treated in 914 patients at the University of Louisville over a nine-year period. Of these fractures, 240 (group 1) received only systemic antibiotic prophylaxis and 845 (group 2) were managed by the supplementary local use of aminoglycoside-polymethylmethacrylate (PMMA) beads. There were no significant differences in age, gender, fracture type, fracture location or follow-up between the two groups. All had copious wound irrigation, meticulous debridement and skeletal stabilisation, but wound management and the use of local antibiotic depended on the surgeons individual preference and there was no randomisation. In group 1 there was an overall infection rate of 12% as against 3.7% in group 2 (p < 0.001). Both acute infection and local osteomyelitis showed a decreased incidence in group 2, but this was statistically significant only in Gustilo type-IIIB and type-IIIC fractures for acute infection, and only in type-II and type-IIIB fractures for chronic osteomyelitis. Our review suggests that the adjuvant use of local antibiotic-laden PMMA beads may reduce the incidence of infection in severe compound fractures.

Factors in pin tract infections.

To determine the factors pertinent to the etiology of pin tract infections, 214 pins in 42 patients were examined prospectively at the time of pin removal. Eighty-nine (41.6%) pin tracts were inflamed, 49 (22.9%) pins had loose anchorages, and 160 (74.8%) pin tips cultured positive for bacteria. The predominant organism cultured was Staphylococcus epidermidis (90.6%), considered nonvirulent, followed by virulent Staphylococcus aureus (37.5%), and Escherichia coli (9.4%). There were 32 loose, inflamed pin tracts. This correlation was statistically significant (P less than .005). There were 40 loose pins whose pin tips had positive cultures. Loose pins correlated for infection with virulent species of bacteria at a highly significant level (P less than .005). Results demonstrate that most pins possess bacterial colonization. Clinically, this means that either inflamed pin tracts or pins with cultures positive for invasive organisms are probably loose and should be removed. Also, mechanical factors are the critical variable in determining the flora of external fixation pins.

Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations.

SummaryBone infection has long been a formidable foe of orthopaedic surgeons. The standard method of treating osteomyelitis generally consists of irrigation and debridement supplemented by pre- and postoperative antibiotics and intraoperative antimicrobial solutions. In the 1970s, Buchholz introduced the concept of local antibacterial therapy in the form of antibiotic impregnated bone cement to treated infected arthroplasties. From this, antibiotic impregnated beads were developed to treat local infections of bone and soft tissue. The advantage of these beads compared with parenteral therapy is that they deliver a high concentration of antibacterial locally while avoiding high systemic concentrations, thus avoiding adverse effects that are often associated with parenteral antibacterial therapy.Additionally, methylmethacrylate bone cement does not significantly affect the immune response of the body. This makes the use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads highly effective either as an alternative to, or in conjunction with, systemic antibiotic treatment of infected arthroplasties, and localised bone and soft tissue infection. This article explores the indications for the use of local therapy as well as any advantages or disadvantages it may have over systemic antibacterial treatment. Additionally, there are important pharmacokinetic considerations for the optimal use of antibacterial agents in the treatment of osteomyelitis.

The prophylactic use of antibiotic impregnated beads in open fractures.

Four hundred four compound fractures were reviewed in 339 patients treated between August 1983 and November 1987. The 252 males and 87 females had a mean age of 33 years (range, 14-86). One hundred twenty-seven (31.4%) fractures were classified as Grade I, 153 (38.9%) as Grade II, and 124 (30.7%) as Grade III by Gustilos classification. The mean Injury Severity Score was 15 (range, 9-57). Three hundred thirty-four of the open fractures (82.7%) were managed with antibiotic-impregnated bead chains (tobramycin) and systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin). Seventy open fractures (17.3%) received systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin) without supplemental use of the antibiotic beads. All open fractures underwent acute irrigation and debridement. In the 404 fractures 46.5% of wounds were closed primarily, 12.9% underwent delayed primary closure, 7.9% were left open, and 32.7% were temporized by the antibiotic bead pouch technique until definitive flap coverage and skin grafting were performed. Of the 404 fractures evaluated, 17 (4.2%) developed an acute wound infection. Of these wound infections, eight (11.4%) were in the group managed with systemic antibiotics alone. By comparison, nine (2.7%) of open fractures treated with combined systemic antibiotics and antibiotic-impregnated beads developed an infection. Chronic osteomyelitis developed in 18 of 404 open fractures (4.5%). Ten (14.3%) open fractures which developed osteomyelitis were managed with systemic antibiotics whereas eight (2.4%) fractures managed with systemic antibiotics and antibiotic-impregnated beads developed a chronic infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of local antibiotic therapy in the management of compound fractures.

Seven hundred four compound fractures (198 [28%] Grade I, 259 [37%] Grade II, and 247 [35%] Grade III) were treated during a seven-year period at the authors institution. One hundred fifty-seven open fractures (22%) (Group A) received systemic antibiotic prophylaxis only, whereas 547 compound fractures (78%) (Group B) were treated with local application of antibiotic beads (tobramycin) in addition to prophylaxis. Fracture grades, age, gender, fracture location, and length of follow-up period were not significantly different between the two groups. All fractures underwent timely irrigation, debridement, and skeletal stabilization. Forty-nine of 704 compound fractures (7%) developed an infection (acute wound infection or chronic osteomyelitis or both). Group A showed an infection rate of 17% (26/157); treatment in Group B resulted in 23 compound fracture infections (4.2%). The difference in the incidence of infection was statistically significant. Comparison of the infection rates in either wound infection or chronic osteomyelitis showed a trend toward decreased rates in Group B versus Group A throughout all fracture grades. However, by subdivision into the fracture grades, only the IIIB types had a statistically significant decrease of infection in Group B versus Group A; the wound infection rate was 39% (9/23) in Group A and 7.3% (7/96) in Group B. The rate of chronic osteomyelitis was 26% (6/23) in Group A and 6.3% (6/96) in Group B. Prophylactic use of antibiotic-laden PMMA beads in addition to systemic antibiotics was of benefit in preventing infectious complications in compound fractures, in particular in Type IIIB open fractures.

The treatment of infected nonunions with gentamicin-polymethylmethacrylate antibiotic beads.

Fifty-two patients enrolled in the Septopal study of infected nonunions were prospectively examined in a randomized, controlled, closed study. Patients were divided into two groups. Group 1 consisted of 24 patients treated with debridement and intravenous antibiotics for four weeks. Group 2 consisted of 28 patients treated with debridement, gentamicin-polymethylmethacrylate (Septopal) beads, and perioperative broad-spectrum parenteral antibiotics. Both groups were treated with similar methods for reconstruction of the nonunions. The demographics of the two groups were similar. The average patient age in Group 1 was 38.4 years, and in Group 2, 37.1 years. Group 1 included 21 men and three women and Group 2, 23 men and five women. The nonunions in both groups ranged from simple hypertrophic nonunions to atrophic unions to segmental defects. The end results were good in both groups. Twenty patients in Group 1 and 25 patients in Group 2 had their infections successfully arrested (83.3% and 89.3%, respectively). Nonunions were successfully healed in the two groups, with similar results (Group 1, 83.3%; Group 2, 85.7%). Infected nonunions responded equally well to either systemic treatment with long-term intravenous antibiotics or local treatment with gentamicin-polymethylmethacrylate beads.

Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures.

Antibiotic-impregnated polymethylmethacrylate (PMMA) beads have been useful in treating orthopedic infections. Local delivery has been reported to establish wound antibiotic levels well above the therapeutic range while avoiding serum levels associated with increased incidence of side effects. After operative debridement, 70 patients with compound fractures were treated prophylactically with tobramycin-impregnated PMMA beads. Observations of antibiotic levels in 27 patients demonstrated antibiotic levels in the wound drainage and clot that were significantly in excess of the usual therapeutic range for tobramycin and simultaneous nontoxic serum levels. Significant levels of tobramycin can be achieved in the extracellular fluid at the fracture site when tobramycin-impregnated PMMA beads are placed in the wound after irrigation and debridement.

Supracondylar femur fractures treated percutaneously.

One hundred twenty-five supracondylar fractures in 118 patients treated with the Green-Seligson-Henry supracondylar intramedullary nail were evaluated. One hundred four patients (111 fractures) were followed up to fracture union. The percutaneous technique was compared with open reduction and internal fixation using the same device. The mean operative time was greater for the open reduction technique when compared with the percutaneous technique (176 minutes versus 76.6 minutes, respectively), as was the mean estimated blood loss (229 cc versus 96.2 cc). The incidence of delayed union was approximately the same for patients who were treated with both techniques. However, the nonunion rate was significantly higher in the patients treated with open reduction and internal fixation than the patients treated with the percutaneous technique (5.6% versus 2.6%). Twenty-nine (39%) patients who were treated with open reduction and internal fixation required bone grafting versus only three (7%) patients who were treated with the percutaneous technique. Additionally, the percutaneous technique did not produce a higher incidence of malalignment and resulted in a greater postoperative range of motion than the open technique. The current study shows that percutaneous treatment of supracondylar femur fractures is possible and can decrease operative times, blood loss, the need for bone grafting, increase rates of union, and improve functional outcomes.

TIMING OF WOUND CLOSURE IN SEVERE COMPOUND FRACTURES

In a consecutive series of 1085 open fractures treated from May 1983 to July 1992, 381 severe compound fractures in 335 patients were managed with the antibiotic bead pouch technique. There were 27 grade I (marked swelling, compartment syndrome), 115 grade II, and 239 grade III open fractures (94 type IIIA, 114 type IIIB, and 31 type IIIC). These fractures were managed with early administration of broad spectrum antibiotics, copious wound irrigation, serial debridements, and external skeletal stabilization. Tobramycin-PMMA beads were placed in the wound, and porous plastic film (Opsite, Smith and Nephew Medical, Limited, Hall, England) covered the soft tissue defect. This dressing was changed every 48 to 72 hours until wound coverage/closure could be obtained. Infection rate, either on an acute or chronic basis, was 2.6% in grade II open fractures and 8.4% in grade III compound fractures. There was no infected wound or bone in the grade I category. Those fractures that did not develop an infection were closed at a mean time of 7.6 days; those that developed an infection were closed at a mean time of 17.9 days. The difference was statistically significant (P < 0.001). When severe open fractures are managed with the antibiotic bead pouch technique, wound closure should be obtained within 1 week to prevent infectious complications.

Antibiotic-leaching from polymethylmethacrylate beads.

Aminoglycoside-impregnated polymethylmethacrylate beads, which are used to deliver antibiotic directly to infected sites in the musculoskeletal system, are available as a manufactured product or they can be mold-made by a pharmacy or hand-rolled by the orthopaedist in the operating suite. We investigated the leaching of antibiotic from each of these types of beads. Our hypothesis was that the elutions of antibiotic from the three types of beads are similar. Three study groups (hand-made, mold-made, and manufactured beads), each composed of four five-bead subsets, were formed so that twenty beads of each type were tested. Each bead was leached daily in a two-milliliter aliquot of normal saline solution throughout a sixty-day period, and the aminoglycoside concentration in twenty of these aliquots was determined. Analysis of variance showed no statistically significant differences when the antibiotic elutions within each subset, between the different subsets, and between the three groups were compared. The clinically important finding of this investigation is that the leaching characteristics of the three types of aminoglycoside-impregnated beads are equivalent when the beads have been fabricated out of comparable materials.