Mycological culture is the traditional method for identifying infecting agents of onychomycosis despite high false-negative results, slower processing, and complications surrounding nondermatophyte mold (NDM) infections. Molecular polymerase chain reaction (PCR) methods are faster and suited for ascertaining NDM infections.
To measure agreement between culture and PCR methods for identification of infecting species of suspected onychomycosis, single toenail samples from 167 patients and repeated serial samples from 43 patients with suspected onychomycosis were processed by culture and PCR for identification of 16 dermatophytes and five NDMs. Agreement between methods was quantified using the kappa statistic (κ).
The methods exhibited fair agreement for the identification of all infecting organisms (single samples: κ = 0.32; repeated samples: κ = 0.38). For dermatophytes, agreement was moderate (single samples: κ = 0.44; repeated samples: κ = 0.42). For NDMs, agreement was poor with single samples (κ = 0.16) but fair with repeated samples (κ = 0.25). Excluding false-negative reports from analyses improved agreement between methods in all cases except the identification of NDMs from single samples.
Culture was three or four times more likely to report a false-negative result compared with PCR. The increased agreement between methods observed by excluding false-negative reports statistically clarifies and highlights the major discord caused by false-negative cultures. The increased agreement of NDM identification from poor to fair with repeated sampling along with their poor agreement in the single samples, with and without false-negatives, affirms the complications of NDM identification and supports the recommendation that serial samples help confirm the diagnosis of NDM infections.
Selecting empirical therapy for a diabetic foot infection (DFI) requires knowing how likely infection with Pseudomonas aeruginosa is in a particular patient. We designed this study to define the risk factors associated with P aeruginosa in DFI.
We performed a preplanned microbiological subanalysis of data from a study assessing the effects of treatment with intralesional epidermal growth factor for diabetic foot wounds in patients in Turkey between January 1, 2012, and December 31, 2013. Patients were screened for risk factors, and the data of enrolled individuals were recorded in custom-designed patient data forms. Factors affecting P aeruginosa isolation were evaluated by univariate and multivariate logistic regression analyses, with statistical significance set at P < .05.
There were 174 patients enrolled in the main study. Statistical analysis was performed in 90 evaluable patients for whom we had microbiological assessments. Cultures were sterile in 19 patients, and 89 bacterial isolates were found in the other 71. The most frequently isolated bacteria were P aeruginosa (n = 23, 25.8%) and Staphylococcus aureus (n = 12, 13.5%). Previous lower-extremity amputation and a history of using active wound dressings were the only statistically significant independent risk factors for the isolation of P aeruginosa in these DFIs.
This retrospective study provides some information on risk factors for infection with this difficult pathogen in patients with DFI. We need prospective studies in various parts of the world to better define this issue.
Diabetic foot infection (DFI) is a serious, difficult-to-treat infection, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower response rates in MRSA skin infections have been reported. This analysis assessed the outcome and safety of daptomycin therapy in patients with a DFI caused by MRSA.
Using the Cubicin Outcomes Registry and Experience and the European Cubicin Outcomes Registry and Experience (2006–2009), 79 patients with MRSA DFI were identified and included in this analysis.
In the 74 evaluable patients, daptomycin was administered at a median dose of 4.8 mg/kg primarily every 24 hours (85.1%) and for a median of 15.0 days. Overall, 77.0% of the patients (57 of 74) received initial therapy with activity against MRSA; however, of patients receiving daptomycin as second-line therapy (n = 31), only 45.2% were treated with an antibiotic agent active against MRSA. The overall clinical success and treatment failure rates were 89.2% and 10.8%, respectively. Success with daptomycin therapy was higher in patients who had surgery and in those whose initial therapy was daptomycin. Eleven patients had 14 adverse events, two of which were possibly related to daptomycin use and led to discontinuation.
In a large real-world cohort of patients with MRSA DFI, daptomycin therapy was shown to be generally well tolerated and effective. The use of an anti-MRSA antibiotic agent should be considered when implementing first-line antibiotic drug therapy for DFI in countries where MRSA is common to avoid inappropriate empirical treatment and potential negative effects on outcomes.
Onychomycosis is estimated to occur in approximately 10% of the global population, with most cases caused by Trichophyton rubrum. Some persistent onychomycosis is caused by mixed infections of T rubrum and one or more co-infecting nondermatophyte molds (NDMs). In onychomycosis, T rubrum strain types may naturally switch and may also be triggered to switch in response to antifungal therapy. T rubrum strain types in mixed infections of onychomycosis have not been characterized.
T rubrum DNA strains in mixed infections of onychomycosis containing co-infecting NDMs were compared with a baseline North American population through polymerase chain reaction amplification of ribosomal DNA tandemly repetitive subelements (TRSs) 1 and 2. The baseline DNA strain types were determined from 102 clinical isolates of T rubrum. The T rubrum DNA strain types from mixed infections were determined from 63 repeated toenail samples from 15 patients.
Two unique TRS-2 types among the clinical isolates contributed to four unique TRS-1 and TRS-2 strain types. Six TRS-1 and TRS-2 strain types represented 92% of the clinical isolates of T rubrum. Four TRS-1 and TRS-2 strain types accounted for 100% of the T rubrum within mixed infections.
Four unique North American T rubrum strains were identified. In support of a shared ancestry, the T rubrum DNA strain types found in mixed infections with NDMs were among the most abundant types. A population of T rubrum strains in mixed infections of onychomycosis has been characterized, with more than one strain detected in some nails. The presence of a co-infecting NDM in mixed infections may contribute to failed therapy by stabilizing the T rubrum strain type, possibly preventing the antifungal therapy–induced strain type switching observed with infections caused by T rubrum alone.
Tedizolid phosphate, the prodrug of the oxazolidinone tedizolid, has been approved in a number of countries, including the United States, those in the European Union, and Canada, for treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Two phase 3 trials demonstrated the noninferior efficacy of tedizolid (200 mg once daily for 6 days) to linezolid (600 mg twice daily for 10 days) in patients with ABSSSI. Because of the challenges of treating lower-extremity ABSSSI, the efficacy and safety of tedizolid and linezolid for treating lower-extremity versus non–lower-extremity infections were compared.
This was a post hoc analysis of pooled data from patients with lower-extremity infections enrolled in two phase 3 studies, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing tedizolid to linezolid in patients with ABSSSI.
Lower-extremity ABSSSI were present in 40.7% of tedizolid-treated and 42.2% of linezolid-treated patients. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 34.7% of all patients with a baseline causative pathogen. Early clinical responses at 48 to 72 hours and investigator-assessed responses at the post-therapy evaluation were similar between tedizolid and linezolid, regardless of ABSSSI type. With both treatments, the early clinical response was slightly higher in patients with non–lower-extremity infection than in those with lower-extremity ABSSSI (tedizolid, 84.8% versus 77.0%; linezolid, 81.4% versus 76.6%, respectively); however, by the post-therapy evaluation visit, response rates were similar (tedizolid, 87.1% versus 86.3%; linezolid, 86.6% versus 87.2%, respectively). Gastrointestinal adverse events and low platelet counts were observed more frequently with linezolid treatment.
Post-therapy evaluations showed that the clinical response of lower-extremity ABSSSI to tedizolid and linezolid was comparable to that of ABSSSI in other locations. A short 6-day course of once-daily tedizolid was as effective as a 10-day course of twice-daily linezolid in treating patients with lower-extremity ABSSSI.
Reports of mixed infections with nondermatophyte molds (NDMs) and dermatophytes in onychomycosis are rare, possibly owing to the inhibition of NDM growth during traditional culture. We sought to determine the prevalence of mixed infections in onychomycosis using molecular identification.
Molecular analyses were used to identify infecting organisms directly from at least two serial great toenail samples from each of the 44 patients.
Mixed infections were present in 41% of the patients (18 of 44). A single coinfecting NDM was the most common mixed infection and was detected in 34% of patients with onychomycosis (15 of 44), with Fusarium oxysporum present in 14% (6 of 44), Scopulariopsis brevicaulis in 9% (4 of 44), Acremonium spp in 2% (1 of 44), Aspergillus spp in 4.5% (2 of 44), and Scytalidium spp in 4.5% (2 of 44). Mixed infections with two NDMs were found in 7% of patients (3 of 44).
Mixed onychomycosis infections may be more prevalent than previously reported.
Background: We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections. It is widely believed that soft-tissue cultures are adequate in the determination of causative bacteria in patients with diabetic foot osteomyelitis. The culture results of specimens taken concurrently from soft-tissue and bone infections show that the former does not predict the latter with sufficient reliability. We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections.
Methods: Forty-five patients with diabetic foot infections were enrolled in the study. Patients had to have clinically suspected foot lesions of grade 3 or higher on the Wagner classification system. In patients with clinically suspected osteomyelitis, magnetic resonance imaging, scintigraphy, or histopathologic examination were performed. Bone and deep soft tissue specimens were obtained from all patients by open surgical procedures under aseptic conditions during debridement or amputation. The specimens were compared only with the other specimens taken from the same patients.
Results: The results of bone and soft-tissue cultures were identical in 49% (n = 22) of cases. In 11% (n = 5) of cases there were no common pathogens. In 29% (n = 13) of cases there were more pathogens in the soft-tissue specimens; these microorganisms included microbes isolated from bone cultures. In four patients (9%) with culture-positive soft-tissue specimens, bone culture specimens remained sterile. In one patient (2%) with culture-positive bone specimen, soft-tissue specimen remained sterile.
Conclusion: Culture specimens should be obtained from both the bone and the overlying deep soft tissue in patients with suspected osteomyelitis whose clinical conditions are suitable. The decision to administer antibiotic therapy should depend on these results. (J Am Podiatr Med Assoc 98(4): 290–295, 2008)
Background: Prediction of amputation would aid clinicians in the management of diabetic foot infections. We aimed to assess the predictive value of baseline and post-treatment levels of acute phase reactants in the outcome of patients with diabetic foot infections.
Methods: We collected data prospectively during minimum follow-up of 6 months in patients with infected diabetic foot ulcers hospitalized in Dokuz Eylul University Hospital between January 1, 2003, and January 1, 2008. After excluding patients who did not attend the hospital for follow-up visits regularly (n = 36), we analyzed data from 165 foot ulcer episodes.
Results: Limb ischemia and osteomyelitis were much more frequent in patients who underwent amputation. Wagner grade, which assesses ulcer depth and the presence of osteomyelitis or gangrene, was higher in patients who needed amputation. Ulcer size was slightly larger in the amputation group. Baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, white blood cell counts, and platelet counts were significantly elevated in patients who underwent amputation. Albumin levels were significantly suppressed in the amputation group. Univariate analysis showed that a 1-SD increase in baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, and white blood cell counts and a 1-SD decrease in post-treatment albumin levels were significantly associated with increased risk of amputation. Post-treatment C-reactive protein level was strongly associated with amputation risk.
Conclusions: Circulating levels of acute phase reactants were associated with amputation risk in diabetic foot infections. (J Am Podiatr Med Assoc 101(1): 1–6, 2011)
Vancomycin is a common treatment option for skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of MRSA, vancomycin is widely used as empirical therapy. In patients with lower-limb infections, antimicrobial penetration is often reduced because of decreased vascular perfusion. In this study, we evaluated the tissue concentrations of vancomycin in hospitalized patients with lower-limb infections.
An in vivo microdialysis catheter was inserted near the margin of the wound and was perfused with lactated Ringer's solution. Tissue and serum samples were obtained after steady state for one dosing interval. Tissue concentrations were corrected for percentage of in vivo recovery using the retrodialysis technique.
Nine patients were enrolled (mean ± SD: age, 54 ± 19 years; weight, 105.6 ± 31.5 kg). Patients received a mean of 12.8 mg/kg of vancomycin every 12 hours (n = 7), every 8 hours (n = 1), or every 24 hours (n = 1). Mean ± SD steady-state trough vancomycin concentrations in serum and tissue were 11.1 ± 3.3 and 6.0 ± 2.6 μg/mL. The mean ± SD 24-hour free drug areas under the curve for serum and wound were 283.7 ± 89.4 and 232.8 ± 75.7 μg*h/mL, respectively. The mean ± SD tissue penetration ratio was 0.8 ± 0.2.
These data suggest that against MRSA with minimum inhibitory concentrations of 1 μg/mL or less, vancomycin achieved blood pharmacodynamic targets required for the likelihood of success. Reduced concentrations may contribute to poor outcomes and the development of resistance. As other literature suggests, alternative agents may be needed when the pathogen of interest has a minimum inhibitory concentration greater than 1 μg/mL.
Diabetic foot ulcers combined with ischemia and infection can be difficult to treat. Few studies have quantified the level of blood supply and infection control required to treat such complex diabetic foot ulcers. We aimed to propose an index for ischemia and infection control in diabetic chronic limb-threatening ischemia (CLTI) with forefoot osteomyelitis.
We retrospectively evaluated 30 patients with diabetic CLTI combined with forefoot osteomyelitis who were treated surgically from January 2009 to December 2016. After 44 surgeries, we compared patient background (age, sex, hemodialysis), infection status (preoperative and 1- and 2-week postoperative C-reactive protein [CRP] levels), surgical bone margin (with or without osteomyelitis), vascular supply (skin perfusion pressure), ulcer size (wound grade 0–3 using the Society for Vascular Surgery Wound, Ischemia, and foot Infection classification), and time to wound healing between patients with healing ulcers and those with nonhealing ulcers.
Preoperative CRP levels and the ratio of ulcers classified as wound grade 3 were significantly lower and skin perfusion pressure was significantly higher in the healing group than in the nonhealing group (P < .05). No other significant differences were found between groups.
This study demonstrates that debridement should be performed first to control infection if the preoperative CRP level is greater than 40 mg/L. Skin perfusion pressure of 55 mm Hg is strongly associated with successful treatment. We believe that this research could improve the likelihood of salvaging limbs in patients with diabetes with CLTI.