Feature Papers in Therapy of Diabetic Foot Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 17257

Special Issue Editors


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Guest Editor
Infectiology and Infection Control, Orthopedic Department, Balgrist University Hospital, Zurich, Switzerland
Interests: prevention and treatment of orthopedic infections, including diabetic foot infections

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Guest Editor
1. Department of Infectious Diseases, Hospital Universitari de Bellvitge. Barcelona; C/ Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain
2. Infectiology and Infection Control, Balgrist University Hospital, Zurich, Switzerland
Interests: diabetic foot infections; orthopedic infections

Special Issue Information

Dear Colleagues,

Diabetic foot infections (DFIs), soft tissue infections and osteomyelitis alike are multifaceted diseases. Usually, the infection is the tip of the iceberg of a larger, chronic, underlying problem. Hence, the management of all DFIs is multidisciplinary and includes the use of antibiotics, surgery, professional wound care and podiatry, adequate off-loading, re-vascularization, the patient's participation, glycemic control, and many other aspects such as the availability of nationwide policies, guidelines, or local financial and organizational resources. The burden that DFIs represent is high and is expected to rise in the future in virtually every region worldwide

Diabetic foot infections probably represent one of the largest fields of medicine with recurrent antibiotic overuse in relation to their moderate and short-term benefits. There are multiple reasons why therapy fails, ranging from the lack of compliance with off-loading, inadequate debridement, ischemia, the occurrence of a new infection, and the selection of new pathogens, to the recurrence of infection with the same pathogens as those present in a previous episode. However, only true recurrences of infection can definitively be prevented by the use of antibiotic treatment.

Although there is a rising number of scientific publications regarding antibiotic treatments for various subsets of DFI, questions remain: the use of oral versus intravenous versus local antibiotics; the optimal duration of systemic antibiotic therapy, the need for biofilm-acting agents; the costs and side effects of antibiotic use; the promotion of antibiotic resistance through from DFI treatments; as well as difficulties in terms of reimbursement and healthcare policies, which may vary from one country to the other and compromise the overall success of DFI management on a large scale.. Finally, antibiotic stewardship in the DFI population may also include non-antibiotic, diagnostic, and therapeutic measures. This Special Issue addresses these issues in line with antibiotic management in DFIs.

Prof. Dr. Ilker Uckay
Dr. Laura Soldevila
Guest Editors

Manuscript Submission Information

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Keywords

  • diabetic foot infection
  • diabetic foot osteomyelitis
  • systemic antibiotic therapy
  • local antibiotic therapy
  • side effects
  • treatment success
  • antibiotic stewardship
  • antibiotic policies and difficulties

Published Papers (8 papers)

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Research

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14 pages, 2820 KiB  
Article
Timing of Revascularization and Parenteral Antibiotic Treatment Associated with Therapeutic Failures in Ischemic Diabetic Foot Infections
by Dominique Altmann, Felix W. A. Waibel, Gabor Forgo, Alexandru Grigorean, Benjamin A. Lipsky, Ilker Uçkay and Madlaina Schöni
Antibiotics 2023, 12(4), 685; https://doi.org/10.3390/antibiotics12040685 - 31 Mar 2023
Cited by 1 | Viewed by 1394
Abstract
For ischemic diabetic foot infections (DFIs), revascularization ideally occurs before surgery, while a parenteral antibiotic treatment could be more efficacious than oral agents. In our tertiary center, we investigated the effects of the sequence between revascularization and surgery (emphasizing the perioperative period of [...] Read more.
For ischemic diabetic foot infections (DFIs), revascularization ideally occurs before surgery, while a parenteral antibiotic treatment could be more efficacious than oral agents. In our tertiary center, we investigated the effects of the sequence between revascularization and surgery (emphasizing the perioperative period of 2 weeks before and after surgery), and the influence of administering parenteral antibiotic therapy on the outcomes of DFIs. Among 838 ischemic DFIs with moderate-to-severe symptomatic peripheral arterial disease, we revascularized 608 (72%; 562 angioplasties, 62 vascular surgeries) and surgically debrided all. The median length of postsurgical antibiotic therapy was 21 days (given parenterally for the initial 7 days). The median time delay between revascularization and debridement surgery was 7 days. During the long-term follow-up, treatment failed and required reoperation in 182 DFI episodes (30%). By multivariate Cox regression analyses, neither a delay between surgery and angioplasty (hazard ratio 1.0, 95% confidence interval 1.0–1.0), nor the postsurgical sequence of angioplasty (HR 0.9, 95% CI 0.5–1.8), nor long-duration parenteral antibiotic therapy (HR 1.0, 95% CI 0.9–1.1) prevented failures. Our results might indicate the feasibility of a more practical approach to ischemic DFIs in terms of timing of vascularization and more oral antibiotic use. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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10 pages, 253 KiB  
Article
Effect of Prior Antibiotic Use on Culture Results in People with Diabetes and Foot Osteomyelitis
by Meryl Cinzía Tila Tamara Gramberg, Jarne Marijn Van Hattem, Jacob Albert Dijkstra, Emma Dros, Max Nieuwdorp, Louise Willy Elizabeth Sabelis and Edgar Josephus Gerardus Peters
Antibiotics 2023, 12(4), 684; https://doi.org/10.3390/antibiotics12040684 - 31 Mar 2023
Cited by 2 | Viewed by 2233
Abstract
Background: Antibiotic use prior to biopsy acquisition in people with diabetes and osteomyelitis of the foot (DFO) might influence bacterial yield in cultures or induce bacterial resistance. Obtaining reliable culture results is pivotal to guide antibiotics for conservative treatment of DFO. Methods: We [...] Read more.
Background: Antibiotic use prior to biopsy acquisition in people with diabetes and osteomyelitis of the foot (DFO) might influence bacterial yield in cultures or induce bacterial resistance. Obtaining reliable culture results is pivotal to guide antibiotics for conservative treatment of DFO. Methods: We prospectively analysed cultures of ulcer bed and percutaneous bone biopsies of people with DFO and investigated if antibiotics administered prior to (<2 months up to 7 days) biopsy acquisition led to more negative cultures or increased resistance in virulent bacteria. We calculated relative risks (RR) and 95% confidence intervals (CIs). We stratified analyses according to biopsy type (ulcer bed or bone). Results: We analysed bone and ulcer bed biopsies of 64 people, of whom 29 received prior antibiotics, and found that prior antibiotics did not lead to a higher risk of at least one negative culture (RR 1.3, (CI 0.8–2.0), nor did prior treatment increase the risk of a specific type of negative culture (RR for bone cultures 1.15, (CI 0.75–1.7), RR for ulcer bed cultures 0.92 (CI 0.33–2.6)) or both cultures (RR 1.3 (CI 0.35–4.7), and neither did it increase the risk of antibiotic resistance in the combined bacterial results of ulcer bed and bone cultures (RR 0.64, (CI 0.23–1.8)). Conclusions: Antibiotics administered up to 7 days before obtaining biopsies in people with DFO do not influence culture yield regardless of biopsy type, nor are they associated with more antibiotic resistance. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
12 pages, 938 KiB  
Article
Do Anti-Biofilm Antibiotics Have a Place in the Treatment of Diabetic Foot Osteomyelitis?
by Eric Senneville, Benoit Gachet, Nicolas Blondiaux and Olivier Robineau
Antibiotics 2023, 12(2), 317; https://doi.org/10.3390/antibiotics12020317 - 3 Feb 2023
Viewed by 2514
Abstract
The choice of antibiotic regimens for use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected, while their role is [...] Read more.
The choice of antibiotic regimens for use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected, while their role is reduced but not negligible in the case of surgical options. Some studies have reported the presence of biofilm structures in bone samples taken from patients with diabetic foot osteomyelitis, which raises the question of the place of anti-biofilm antibiotic regimens in this setting. During the last two decades, clinical studies have suggested a potential benefit for anti-biofilm antibiotics, mainly rifampicin against staphylococci and fluoroquinolones against gram-negative bacilli. However, no data from randomized controlled studies have been reported so far. The present work provides a summary of the available data on the question of the place of anti-biofilm antibiotics for the treatment of diabetic foot osteomyelitis, but also the potential limitations of such treatments. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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8 pages, 465 KiB  
Article
Influence of Skin Commensals on Therapeutic Outcomes of Surgically Debrided Diabetic Foot Infections—A Large Retrospective Comparative Study
by Ilker Uçkay, Dan Lebowitz, Benjamin Kressmann, Benjamin A. Lipsky and Karim Gariani
Antibiotics 2023, 12(2), 316; https://doi.org/10.3390/antibiotics12020316 - 3 Feb 2023
Viewed by 1608
Abstract
In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients [...] Read more.
In diabetic foot infections (DFI), the clinical virulence of skin commensals are generally presumed to be low. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria) and pathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pathogenic pathogens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxygen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs. 24 %, p = 0.23) or microbiological recurrence (11% vs. 17 %, p = 0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, the isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confidence interval 0.1–3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may also be based on oral non-beta-lactam antibiotic agents effective against the corresponding skin pathogens. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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11 pages, 630 KiB  
Article
Bacterial Diversity and Antibiotic Resistance in Patients with Diabetic Foot Osteomyelitis
by Francisco Javier Álvaro-Afonso, Yolanda García-Álvarez, Aroa Tardáguila-García, Marta García-Madrid, Mateo López-Moral and José Luis Lázaro-Martínez
Antibiotics 2023, 12(2), 212; https://doi.org/10.3390/antibiotics12020212 - 19 Jan 2023
Cited by 2 | Viewed by 1890
Abstract
This study analysed the bacterial diversity, antibiotic susceptibility, and resistance in patients with complications of diabetic foot osteomyelitis (DFO). A retrospective observational study was carried out between September 2019 and September 2022 and involved 215 outpatients with a diagnosis of DFO at a [...] Read more.
This study analysed the bacterial diversity, antibiotic susceptibility, and resistance in patients with complications of diabetic foot osteomyelitis (DFO). A retrospective observational study was carried out between September 2019 and September 2022 and involved 215 outpatients with a diagnosis of DFO at a specialized diabetic foot unit. A total of 204 positive bone cultures were isolated, including 62.7% monomicrobial cultures, and 37.3% were formed with at least two microorganisms. We observed that Proteus spp., Coagulase-negative staphylococci (CoNS), Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Corynebacterium were the most frequently isolated microorganisms and accounted for more than 10% of the DFO cases. With stratification by Gram-positive (GP) and Gram-negative (GN) bacteria, we observed that 91.6% of cultures presented at least one GP bacteria species, and 50.4% presented at least one GN bacteria species. The most common GP species were CoNS (29%), S. aureus (25.8%), and Corynebacterium spp. (14%). The most frequent GN species consisted of Proteus spp. (32%), P. aeruginosa (23.3%), and E. coli (17.5%). The main antibiotics with resistance to GP-dominated infections were penicillins without β-lactamase inhibitor, and those in GN-dominated infections were sulfonamides and penicillins without β-lactamase. Significant differences were not observed in mean healing time in DFU with acute osteomyelitis (12.76 weeks (4.50;18)) compared to chronic osteomyelitis (15.31 weeks (7;18.25); p = 0.101) and when comparing cases with soft tissue infection (15.95 (6;20)) and those without such an infection (16.59 (7.25;19.75), p = 0.618). This study shows that when treatment of DFO is based on early surgical treatment, the type of DFO and the presence of soft infection are not associated with different or worse prognoses. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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Review

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21 pages, 333 KiB  
Review
The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature
by Laura Soldevila-Boixader, Oscar Murillo, Felix W. A. Waibel, Tanja Huber, Madlaina Schöni, Rahim Lalji and Ilker Uçkay
Antibiotics 2023, 12(4), 774; https://doi.org/10.3390/antibiotics12040774 - 18 Apr 2023
Cited by 1 | Viewed by 1709
Abstract
The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative [...] Read more.
The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative review was to summarize the most frequent and most severe AEs reported in prospective trials and observational studies at the global level in DFI. Gastrointestinal intolerances were the most frequent AEs, from 5% to 22% among all therapies; this was more common when prolonged antibiotic administration was combined with oral beta-lactam or clindamycin or a higher dose of tetracyclines. The proportion of symptomatic colitis due to Clostridium difficile was variable depending on the antibiotic used (0.5% to 8%). Noteworthy serious AEs included hepatotoxicity due to beta-lactams (5% to 17%) or quinolones (3%); cytopenia’s related to linezolid (5%) and beta-lactams (6%); nausea under rifampicin, and renal failure under cotrimoxazole. Skin rash was found to rarely occur and was commonly associated with the use of penicillins or cotrimoxazole. AEs from prolonged antibiotic use in patients with DFI are costly in terms of longer hospitalization or additional monitoring care and can trigger additional investigations. The best way to prevent AEs is to keep the duration of antibiotic treatment short and with the lowest dose clinically necessary. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
15 pages, 649 KiB  
Review
Local Antibiotics in the Treatment of Diabetic Foot Infections: A Narrative Review
by Laura Soldevila-Boixader, Alberto Pérez Fernández, Javier Muñoz Laguna and Ilker Uçkay
Antibiotics 2023, 12(1), 124; https://doi.org/10.3390/antibiotics12010124 - 9 Jan 2023
Cited by 6 | Viewed by 3686
Abstract
Along with the increasing global burden of diabetes, diabetic foot infections (DFI) and diabetic foot osteomyelitis (DFO) remain major challenges for patients and society. Despite progress in the development of prominent international guidelines, the optimal medical treatment for DFI and DFO remains unclear [...] Read more.
Along with the increasing global burden of diabetes, diabetic foot infections (DFI) and diabetic foot osteomyelitis (DFO) remain major challenges for patients and society. Despite progress in the development of prominent international guidelines, the optimal medical treatment for DFI and DFO remains unclear as to whether local antibiotics, that is, topical agents and local delivery systems, should be used alone or concomitant to conventional systemic antibiotics. To better inform clinicians in this evolving field, we performed a narrative review and summarized key relevant observational studies and clinical trials of non-prophylactic local antibiotics for the treatment of DFI and DFO, both alone and in combination with systemic antibiotics. We searched PubMed for studies published between January 2000 and October 2022, identified 388 potentially eligible records, and included 19 studies. Our findings highlight that evidence for adding local antibiotic delivery systems to standard DFO treatment remains limited. Furthermore, we found that so far, local antibiotic interventions have mainly targeted forefoot DFO, although there is marked variation in the design of the included studies. Suggestive evidence emerging from observational studies underscores that the addition of local agents to conventional systemic antibiotics might help to shorten the clinical healing time and overall recovery rates in infected diabetic foot ulcers, although the effectiveness of local antibiotics as a standalone approach remains overlooked. In conclusion, despite the heterogeneous body of evidence, the possibility that the addition of local antibiotics to conventional systemic treatment may improve outcomes in DFI and DFO cannot be ruled out. Antibiotic stewardship principles call for further research to elucidate the potential benefits of local antibiotics alone and in combination with conventional systemic antibiotics for the treatment of DFI and DFO. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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Other

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8 pages, 840 KiB  
Perspective
Potential Utility of Ultrasound-Enhanced Delivery of Antibiotics, Anti-Inflammatory Agents, and Nutraceuticals: A Mini Review
by J. Karim Ead, Arjun Sharma, Miranda Goransson and David G. Armstrong
Antibiotics 2022, 11(10), 1290; https://doi.org/10.3390/antibiotics11101290 - 22 Sep 2022
Viewed by 1618
Abstract
Ultrasound technology has therapeutic properties that can be harnessed to enhance topical drug delivery in a process known as phonophoresis. The literature on this method of drug delivery is currently sparse and scattered. In this review, we explore in vivo and in vitro [...] Read more.
Ultrasound technology has therapeutic properties that can be harnessed to enhance topical drug delivery in a process known as phonophoresis. The literature on this method of drug delivery is currently sparse and scattered. In this review, we explore in vivo and in vitro controlled trials as well as studies detailing the mechanism of action in phonophoresis to gain a clearer picture of the treatment modality and explore its utility in chronic wound management. Upon review, we believe that phonophoresis has the potential to aid in chronic wound management, particularly against complicated bacterial biofilms. This would offer a minimally invasive wound management option for patients in the community. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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