Research

12 pages, 1412 KiB

Open AccessArticle

What Factors Affect Outcome in the Treatment of Fracture-Related Infection?

by Martin McNally, Ruth Corrigan, Jonathan Sliepen, Maria Dudareva, Rob Rentenaar, Frank IJpma, Bridget L. Atkins, Marjan Wouthuyzen-Bakker and Geertje Govaert

Antibiotics 2022, 11(7), 946; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11070946 - 14 Jul 2022

Cited by 11 | Viewed by 1809

Abstract

This international, multi-center study investigated the effect of individual components of surgery on the clinical outcomes of patients treated for fracture-related infection (FRI). All patients with surgically treated FRIs, confirmed by the FRI consensus definition, were included. Data were collected on demographics, time [...] Read more.

This international, multi-center study investigated the effect of individual components of surgery on the clinical outcomes of patients treated for fracture-related infection (FRI). All patients with surgically treated FRIs, confirmed by the FRI consensus definition, were included. Data were collected on demographics, time from injury to FRI surgery, soft tissue reconstruction, stabilization and systemic and local anti-microbial therapy. Patients were followed up for a minimum of one year. In total, 433 patients were treated with a mean age of 49.7 years (17–84). The mean follow-up time was 26 months (range 12–72). The eradication of infection was successful in 86.4% of all cases and 86.0% of unhealed infected fractures were healed at the final review. In total, 3.3% required amputation. The outcome was not dependent on age, BMI, the presence of metalwork or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p = 0.52). The debridement and retention of a stable implant (DAIR) had a failure rate of 21.4%; implant exchange to a new internal fixation had a failure rate of 12.5%; and conversion to external fixation had a failure rate of 10.3% (adjusted hazard ratio (aHR) DAIR vs. Ext Fix 2.377; 95% C.I. 0.96–5.731). Tibial FRI treated with a free flap was successful in 92.1% of cases and in 80.4% of cases without a free flap (HR 0.38; 95% C.I. 0.14–1.0), while the use of NPWT was associated with higher recurrence rates (HR 3.473; 95% C.I. 1.852–6.512). The implantation of local antibiotics reduced the recurrence from 18.7% to 10.0% (HR 0.48; 95% C.I. 0.29–0.81). The successful treatment of FRI was multi-factorial. These data suggested that treatment decisions should not be based on time from injury alone, as other factors also affected the outcome. Further work to determine the best indications for DAIR, free flap reconstruction and local antibiotics is warranted. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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12 pages, 648 KiB

Open AccessArticle

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections

by Ruth A. Corrigan, Jonathan Sliepen, Maria Dudareva, Frank F. A. IJpma, Geertje Govaert, Bridget L. Atkins, Rob Rentenaar, Marjan Wouthuyzen-Bakker and Martin McNally

Antibiotics 2022, 11(7), 943; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11070943 - 14 Jul 2022

Cited by 12 | Viewed by 1426

Abstract

Fracture-related infections (FRIs) are classically considered to be early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially [...] Read more.

Fracture-related infections (FRIs) are classically considered to be early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially reserved for early FRI. This study examined pathogens isolated from FRI to confirm or refute these hypothesized differences in causative pathogens over time. Cases of FRI managed surgically at three centres between 2015–2019 and followed up for at least one year were included. Data were analysed regarding patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analysed separately. In total, 433 FRIs were studied, including 51 early cases (median time from injury of 2 weeks, interquartile range (IQR) of 1–2 weeks), 82 delayed cases (median time from injury of 5 weeks, IQR of 4–8 weeks) and 300 late cases (median time from injury of 112 weeks, IQR of 40–737 weeks). The type of infection was associated with time since injury; early or delayed FRI are most likely to be polymicrobial, whereas late FRIs are more likely to be culture-negative, or monomicrobial. Staphylococcus aureus was the most commonly isolated pathogen at all time points; however, we found no evidence that the type of pathogens isolated in early, delayed or late infections were different (p = 0.2). More specifically, we found no evidence for more virulent pathogens (S. aureus, Gram-negative aerobic bacilli) in early infections and less virulent pathogens (such as coagulase negative staphylococci) in late infections. In summary, decisions on FRI treatment should not assume microbiological differences related to time since injury. From a microbiological perspective, the relevance of classifying FRI by time since injury remains unclear. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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10 pages, 674 KiB

Open AccessArticle

Efficacy of Infection Eradication in Antibiotic Cement-Coated Intramedullary Nails for Fracture-Related Infections, Nonunions, and Fusions

by Janet D. Conway, Ahmed H. Elhessy, Selin Galiboglu, Nirav Patel and Martin G. Gesheff

Antibiotics 2022, 11(6), 709; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11060709 - 25 May 2022

Cited by 3 | Viewed by 2018

Abstract

Antibiotic cement-coated intramedullary nails (ACCINs) are increasing in popularity as a viable solution for the treatment of fracture-related infections (FRIs), infected long bone nonunions, and arthrodeses without an external fixator. ACCINs effectively manage to fulfill three of the basic principles for eradicating osteomyelitis: [...] Read more.

Antibiotic cement-coated intramedullary nails (ACCINs) are increasing in popularity as a viable solution for the treatment of fracture-related infections (FRIs), infected long bone nonunions, and arthrodeses without an external fixator. ACCINs effectively manage to fulfill three of the basic principles for eradicating osteomyelitis: dead space management, antibiotic delivery, and bone stability. We performed a retrospective review of 111 patients who were treated with ACCINs between January 2014 and December 2020. In our series, 87.4% (n = 97) of patients achieved healed and uninfected bone or stable arthrodesis at a mean follow-up of 29.2 months (range, 6–93 months). Additionally, 69.1% (n = 67) of healed patients were resolved after only one procedure, and the remainder (30.9%, n = 30) healed after one or more additional procedures. The mean number of additional procedures was 2.1 (range, 1–6 additional procedures). The overall limb salvage rate was 93.7% (n = 104). The majority of the total cohort were successfully treated in only one surgery. This study suggests that ACCINs are effective in the treatment of FRIs, infected long bone nonunions, and infected ankle and knee arthrodeses. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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11 pages, 998 KiB

Open AccessArticle

Tobramycin Blood Levels after Local Antibiotic Treatment of Bone and Soft Tissue Infection

by Carlos D. Pargas, Ahmed H. Elhessy, Mehdi Abouei, Martin G. Gesheff and Janet D. Conway

Antibiotics 2022, 11(3), 336; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030336 - 04 Mar 2022

Cited by 5 | Viewed by 2242

Abstract

Local antibiotic delivery using different carriers plays an important role in both infection prophylaxis and treatment. Besides dead space management, these carriers have the advantage of providing a high concentration of local antibiotics with a lower risk of systemic toxicity. Few studies have [...] Read more.

Local antibiotic delivery using different carriers plays an important role in both infection prophylaxis and treatment. Besides dead space management, these carriers have the advantage of providing a high concentration of local antibiotics with a lower risk of systemic toxicity. Few studies have reported on systemic toxicity associated with antibiotic-impregnated carriers. The present study investigates the systemic tobramycin concentration at 24, 48 and 72 h postoperatively after using tobramycin-loaded polymethyl methacrylate (PMMA) and calcium sulfate (CS) as local antibiotic carriers. Additionally, this work assesses the renal function postoperatively for indications of acute kidney injury (AKI). Fifty-two patients were treated in 58 procedures with tobramycin and vancomycin-loaded PMMA, CS, or both. All systemic tobramycin levels were <2 mcg/mL at 72 h, and the resulting rate of AKI was 12% (7/58). In conclusion, local tobramycin antibiotic delivery using PMMA, CS, or both remains a safe and effective modality in the treatment of osteomyelitis as long as the surgeon is aware of its possible nephrotoxic effect. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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11 pages, 1341 KiB

Open AccessArticle

What Is the Most Effective Empirical Antibiotic Treatment for Early, Delayed, and Late Fracture-Related Infections?

by Susanne Baertl, Nike Walter, Ulrike Engelstaedter, Martin Ehrenschwender, Florian Hitzenbichler, Volker Alt and Markus Rupp

Antibiotics 2022, 11(3), 287; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030287 - 22 Feb 2022

Cited by 16 | Viewed by 2494

Abstract

Antibiotic treatment strategies for fracture-related infections (FRI) are often extrapolated from periprosthetic joint infections (PJI), although, in contrast to PJI, detailed analysis of pathogens and their antibiotic resistance is missing. Therefore, this study aimed to investigate antibiotic susceptibility profiles to identify effective empiric [...] Read more.

Antibiotic treatment strategies for fracture-related infections (FRI) are often extrapolated from periprosthetic joint infections (PJI), although, in contrast to PJI, detailed analysis of pathogens and their antibiotic resistance is missing. Therefore, this study aimed to investigate antibiotic susceptibility profiles to identify effective empiric antibiotic treatment for early-, delayed-, and late-onset FRI. Patients treated for FRI from 2013 to 2020 were grouped into early (<2 weeks), delayed (3–10 weeks), and late (>10 weeks) onset of infection. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. In total, 117 patients (early n = 19, delayed n = 60, late n = 38) were enrolled. In early-onset FRI, 100.0% efficacy would be achieved by meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide, ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide. For patients with delayed FRI, the highest susceptibility was revealed for meropenem + vancomycin, gentamicin + vancomycin and ciprofloxacin + glycopeptide (96.7%). Meropenem + vancomycin was the most effective empiric antimicrobial in patients with late-onset of infection with 92.1% coverage. No subgroup differences in antibiotic sensitivity profiles were observed except for the combination ciprofloxacin + glycopeptide, which was significantly superior in early FRI (F = 3.304, p = 0.04). Across all subgroups meropenem + vancomycin was the most effective empiric treatment in 95.7% of patients with confirmed susceptibility. Meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide are the best therapeutic options for FRI, regardless of the onset of infection. To avoid multidrug resistance, established antibiotic combinations such as co-amoxiclav with a glycopeptide seem to be reasonable as a systemic antibiotic therapy, while vancomycin + gentamicin could be implemented in local antibiotic therapy to reduce adverse events during treatment. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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Review

Jump to: Research, Other

36 pages, 1572 KiB

Open AccessReview

Isavuconazole in the Treatment of Aspergillus fumigatus Fracture-Related Infection: Case Report and Literature Review

by Beatrijs Mertens, Ruth Van Daele, Melissa Depypere, Katrien Lagrou, Yves Debaveye, Joost Wauters, Stefaan Nijs, Willem-Jan Metsemakers and Isabel Spriet

Antibiotics 2022, 11(3), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030344 - 05 Mar 2022

Cited by 3 | Viewed by 2773

Abstract

Aspergillus fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for Aspergillus osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. [...] Read more.

Aspergillus fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for Aspergillus osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. We describe a patient with Aspergillus fumigatus FRI of the tibia who was treated with isavuconazole after developing liver function disturbances during voriconazole therapy. Isavuconazole, the active moiety formed after hydrolysis of the prodrug isavuconazonium sulfate by plasma esterases, was administered in a maintenance dose of 200 mg q24 h, followed by 150 mg q24 h. The patient completed a six-month antifungal treatment course. Although fracture union was not achieved during six months of follow-up after therapy cessation, no confirmatory signs of FRI were observed. Additionally, two literature searches were conducted to review available data on antifungal treatment of Aspergillus osteomyelitis and bone penetration of antifungals. One hundred and eight cases of Aspergillus osteomyelitis, including six (5.6%) FRI cases, were identified. Voriconazole and (lipid formulations of) amphotericin B were the most commonly used antifungals. In three (2.8%) cases isavuconazole was prescribed as salvage therapy. Data on antifungal bone penetration were reported for itraconazole, voriconazole, amphotericin B, anidulafungin and 5-fluorocytosin. Isavuconazole might be a promising alternative for the treatment of Aspergillus osteomyelitis. However, standardized case documentation is needed to evaluate the efficacy of isavuconazole and other antifungals in the treatment of Aspergillus osteomyelitis, including FRI. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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Other

Jump to: Research, Review

18 pages, 614 KiB

Open AccessSystematic Review

Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal

by Femke Goormans, Ruxandra Coropciuc, Maximilien Vercruysse, Isabel Spriet, Robin Willaert and Constantinus Politis

Antibiotics 2022, 11(4), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11040483 - 05 Apr 2022

Cited by 4 | Viewed by 5047

Abstract

Infection after maxillofacial trauma remains an important complication, with a significant socio-economic impact. While consensus exists that systemic antibiotic prophylaxis reduces the risk of infection in the management of maxillofacial fractures, the type, and duration remain controversial. Therefore, the purpose of this scoping [...] Read more.

Infection after maxillofacial trauma remains an important complication, with a significant socio-economic impact. While consensus exists that systemic antibiotic prophylaxis reduces the risk of infection in the management of maxillofacial fractures, the type, and duration remain controversial. Therefore, the purpose of this scoping review was to provide an overview of the current evidence that supports the use of prophylactic antibiotics in the treatment of maxillofacial fractures. A comprehensive literature search on 1 January 2022, in PubMed, Web of Science, Embase, and Cochrane, revealed 16 articles. Most studies focused on the duration of systemic antibiotic prophylaxis and compared a one-day to a five-day regimen. Included studies showed considerable variability in design and research aims, which rendered them difficult to compare. Furthermore, a variety of antibiotic regimens were used, and most studies had a short follow-up period and unclear outcome parameters. This scoping review demonstrates the lack of well-constructed studies investigating the type and duration of systemic antibiotic prophylaxis in the treatment of maxillofacial trauma. Based on the included articles, prolonging antibiotic prophylaxis over 24 h for surgically treated fractures does not appear to be beneficial. Furthermore, there is no evidence for its use in conservatively treated fractures. These results should be interpreted with caution since all included studies had limitations. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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12 pages, 621 KiB

Open AccessSystematic Review

Duration of Perioperative Antibiotic Prophylaxis in Open Fractures: A Systematic Review and Critical Appraisal

by Niels Vanvelk, Baixing Chen, Esther M. M. Van Lieshout, Charalampos Zalavras, T. Fintan Moriarty, William T. Obremskey, Michael H. J. Verhofstad and Willem-Jan Metsemakers

Antibiotics 2022, 11(3), 293; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030293 - 23 Feb 2022

Cited by 4 | Viewed by 3294

Abstract

Fracture-related infection (FRI) remains a serious complication in open fracture care. Adequate surgical treatment and perioperative antibiotic prophylaxis (PAP) are key factors influencing the outcome. However, data concerning the optimal duration of PAP is scarce. The aim of this systematic review was to [...] Read more.

Fracture-related infection (FRI) remains a serious complication in open fracture care. Adequate surgical treatment and perioperative antibiotic prophylaxis (PAP) are key factors influencing the outcome. However, data concerning the optimal duration of PAP is scarce. The aim of this systematic review was to provide an overview of current evidence on the association between PAP duration and FRI in open fractures. A comprehensive search on 13 January 2022, in Embase, Medline, Cochrane, Web of Science and Google Scholar revealed six articles. Most studies compared either 1 day versus 5 days of PAP or included a cut-off at 72 h. Although prolonged PAP was not beneficial in the majority of patients, the variety of antibiotic regimens, short follow-up periods and unclear description of outcome parameters were important limitations that were encountered in most studies. This systematic review demonstrates a lack of well-constructed studies investigating the effect of PAP duration on FRI. Based on the available studies, prolonged PAP does not appear to be beneficial in the prevention of FRI in open fractures. However, these results should be interpreted with caution since all included studies had limitations. Future randomized trials are necessary to answer this research question definitively. Full article

(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)

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