Antibiotic Tissue Penetration in Diabetic Foot Infections

2015 ◽  
Vol 105 (6) ◽  
pp. 520-531 ◽  
Author(s):  
Amanda Ray ◽  
Danielle Malin ◽  
David P. Nicolau ◽  
Dora E. Wiskirchen

Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with diabetic foot infections.

2007 ◽  
Vol 45 (9) ◽  
pp. 2819-2828 ◽  
Author(s):  
D. M. Citron ◽  
E. J. C. Goldstein ◽  
C. V. Merriam ◽  
B. A. Lipsky ◽  
M. A. Abramson

2015 ◽  
Vol 59 (3) ◽  
pp. 1751-1754 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Katie M. Simpson ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
...  

ABSTRACTPexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50and MIC90against all organisms tested from DFI were 16 and 32 μg/ml, respectively.Escherichia coli,Klebsiella pneumoniae,Citrobacter koseri,Enterobacter cloacae,Acinetobacterspecies, andPseudomonas aeruginosaMIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values amongStaphylococcus aureus(methicillin-resistantS. aureus[MRSA] and methicillin-susceptibleS. aureus[MSSA]), beta-hemolytic streptococci, andEnterococcus faeciumranged from 8 to 32 μg/ml. Pexiganan activity was not adversely affected for members of the familyEnterobacteriaceaeorP. aeruginosathat produced β-lactamases or resistance mechanisms to other commonly used antimicrobial agents. Decreased susceptibility to vancomycin did not affect pexiganan activity againstS. aureusorE. faecium.Enterococcus faecalisappears to be intrinsically less susceptible to pexiganan (MIC, 32 to 256 μg/ml). The “all organism” MIC90of 32 μg/ml for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.


GERMS ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 39-51
Author(s):  
Azza A Ismail ◽  
Marwa A Meheissen ◽  
Talaat A Abd Elaaty ◽  
Nermine E Abd-Allatif ◽  
Heba S Kassab

2014 ◽  
Vol 103 ◽  
pp. S27 ◽  
Author(s):  
M. Dehayem ◽  
E. Ngassam ◽  
F. Mendane ◽  
V. Balla ◽  
J. Saji ◽  
...  

2014 ◽  
Vol 21 (1) ◽  
pp. 55-62
Author(s):  
Ioan Marin ◽  
Roxana Zaharia ◽  
Leonard Lupu ◽  
Emilia Rusu ◽  
Gabriela Radulian

Abstract Background and aims: The treatment of diabetic foot complications is combined, surgical and medical. The aim of our study was to assess the results of antimicrobial therapy in diabetic foot infections. Material and methods: 100 patients with diabetic foot infections admitted in the Surgery Clinic “I. Juvara” between December 2010 and February 2011 were analyzed. Results: Mean age at presentation was 58.4±9.74 years for women and 63.2±10.53 years for men. Mean diabetes duration was 12.3 years in men and 15.7 years in women. Patients with peripheral arterial disease represented 45% of cases, patients with neuropathy represented 16% of cases and patients with both conditions 39% of the cases. 41 patients suffered minor surgical interventions, 36 patients experienced minor amputations and 23 major amputations (below or above the knee). Antibiotic treatment included cephalosporins, fluoroquinolones and combinations with Metronidazole. After treatment, 74% of patients had a good postoperative evolution. For 26 patients a change of the antibiotic was necessary but only in 10 cases this was made according to antibiogram. Conclusions: Surgical debridement and wound management, carefully chosen antimicrobial therapy and treatment of comorbidities are very important for a successful outcome. Initial empirical antibiotic selection should be followed by culture-guided definitive therapy.


Author(s):  
DASARAJU RAJESH ◽  
M. V. ADVAITHA ◽  
RAJENDRA HOLLA

Objective: Due to the uncertainty about optimal antibiotic treatment, and probably substantial variation in practice, the present study was carried out to determine the bacterial profiles of infected diabetic foot ulcers (DFUs) and also to analyze the prescribing pattern of antibiotics used. Methods: A prospective observational study was carried out in the department of General surgery at a tertiary care teaching hospital, Mangalore. Demographic details and treatment data of 78 patients were collected in a specially designed Proforma, and the data were analyzed using Microsoft Excel. Results: According to Meggit-Wagner's classification, patients admitted with DFUs predominantly belonged to WAGNER 1 category (36%), followed by WAGNER 4 (26%) and WAGNER 2 (22%) categories. Out of 66 culture-positive specimens, 21 (31.8%) had monomicrobial flora, and 45 (68.2%) had polymicrobial flora. A total of 148 organisms were obtained from the specimens. The most common isolates were Staphylococcus aureus (22.3%) and Pseudomonas aeruginosa (17.5%). Ceftriaxone was the most commonly prescribed empirical antibiotic (29%), followed by linezolid (20%), piperacillin-tazobactam (20%), amoxicillin-clavulanic acid (13%), cefoperazone-sulbactam (11%). After the culture and sensitivity (C/S) results, antimicrobials were changed in 74.61% of patients in the preference of Linezolid (51%), Amikacin (27%), Levofloxacin (19%), Ciprofloxacin (17%), Piperacillin-tazobactam (13%), Cefixime (15%), Ceftriaxone (11%) among others. Clindamycin and metronidazole were used to cover anaerobic microorganisms. Conclusion: Most of the microorganisms isolated from DFUs were resistant to many types of antibiotics. Gram-positive organisms were largely sensitive to linezolid and vancomycin, while Gram-negative organisms to amikacin and imipenem. Local treatment of wounds is essential.


The Foot ◽  
2006 ◽  
Vol 16 (3) ◽  
pp. 158-164 ◽  
Author(s):  
A.K. Ako-Nai ◽  
I.C. Ikem ◽  
O.O. Akinloye ◽  
A.O. Aboderin ◽  
R.T. Ikem ◽  
...  

2011 ◽  
Vol 55 (9) ◽  
pp. 4170-4175 ◽  
Author(s):  
Dora E. Wiskirchen ◽  
Ashley Shepard ◽  
Joseph L. Kuti ◽  
David P. Nicolau

ABSTRACTStaphylococcus aureusand other Gram-positive organisms, including methicillin-resistantS. aureus, continue to be the predominant pathogens associated with diabetic foot infections. Consequently, linezolid is often used to treat these infections. The purpose of the current study was to describe the pharmacokinetic profile and determine the level of penetration of linezolid into healthy thigh tissue and infected wound tissue of the same extremity in 9 diabetic patients with chronic lower limb infections by use ofin vivomicrodialysis. Hourly plasma and dialysate samples were obtained over a 12-h dosing interval following 3 to 4 doses of linezolid (600 mg intravenously every 12 h). Plasma protein binding was also assessed at 1, 6, and 12 h postdose. The means ± standard deviations (SD) for the maximum concentration in serum (Cmax), the volume of distribution at terminal phase (Vz), and the half-life (t1/2) for linezolid in plasma were 11.99 ± 3.67 μg/ml, 0.71 ± 0.25 liters/kg of body weight, and 4.71 ± 1.23 h, respectively. Mean protein binding was 14.78% (range, 3.85 to 32.03%). The mean areas under the concentration-time curves from 0 to 12 h for the free, unbound fraction of linezolid (fAUC0–12values) ± SD for plasma, wound tissue, and thigh tissue were 51.24 ± 12.72, 82.76 ± 59.01, and 92.52 ± 60.44 μg · h/ml, respectively. Tissue penetration ratios (tissuefAUC to plasmafAUC) were similar for thigh (1.42; range, 1.08 to 2.23) and wound (1.27; range, 0.86 to 2.26) tissues (P= 0.648). With the currently approved dosing regimen, linezolid penetrated well into both healthy thigh tissue and infected wound tissue in these diabetic patients.


Sign in / Sign up

Export Citation Format

Share Document