The sodium-glucose cotransporter-2 inhibitor canagliflozin does not increase risk of non-genital skin and soft tissue infections in people with type 2 diabetes mellitus: A pooled post hoc analysis from the CANVAS Program and CREDENCE randomized double-blind trials.

AIMS: To assess whether the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin affects risk of non-genital skin and soft tissue infections (SSTIs). MATERIALS AND METHODS: We performed a post hoc pooled individual participant analysis of the CANVAS Program and CREDENCE trials that randomized people with type 2 diabetes at high cardiovascular risk and/or with chronic kidney disease to either canagliflozin or placebo. Investigator-reported adverse events were assessed by two blinded authors following predetermined criteria for non-genital SSTIs. Risks of non-genital SSTIs, overall and within prespecified subgroups, and risk of non-genital fungal SSTIs, were analysed using Cox regression models. Factors associated with non-genital SSTIs were assessed using multivariable Cox regression models. RESULTS: Overall, 903 of 14 531 participants (6%) experienced non-genital SSTIs over a median follow-up of 26 months. No difference was observed in non-genital SSTI rates between canagliflozin and placebo (24.0 events/1000 person-years vs. 23.9 events/1000 person-years, respectively; hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.85-1.11; P = 0.70), with consistent results across subgroups (all P interaction > 0.05). The risk of recurrent events and non-genital fungal infection also did not differ significantly between canagliflozin and placebo (HR 1.06, 95% CI 0.94-1.19 [P = 0.32] and HR 1.18, 95% CI 0.88-1.60 [P = 0.27], respectively). Baseline factors independently associated with non-genital SSTIs were younger age, male sex, higher body mass index, higher glycated haemoglobin, lower estimated glomerular filtration rate (eGFR), established peripheral vascular disease, and history of neuropathy. CONCLUSIONS: Canagliflozin did not affect risk of non-genital SSTIs or non-genital fungal SSTIs compared with placebo. These findings suggest that any SGLT2 inhibitor-mediated change in skin microenvironment is unlikely to have meaningful clinical consequences.

Contezolid in complicated skin and soft tissue infection.

Contezolid (MRX-I, Youxitai) is an oral oxazolidinone drug being developed by MicuRx Pharmaceutical Co., Ltd., Shanghai, China. It was approved by China's National Medical Products Administration (NMPA) in June 2021, attaining its first approval for the treatment of complicated skin and soft tissue infections (cSSTIs). It is also under clinical development for acute bacterial skin and skin structure infections (ABSSSIs) in the U.S. after receiving qualified infectious disease product (QIDP) classification and fast track status by U.S. Food and Drug Administration (FDA) in September 2018. Contezolid is effective against a broad range of Gram-positive bacteria including activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococci (VRE). It provides a major benefit over the most popular drug of its class, linezolid (Zyvox), by offering an improved safety profile and minimal effects concerning myelosuppression and monoamine oxidase (MAO) inhibition, two independent adverse events limiting linezolid use in the clinic. The recommended dosage regimen of contezolid is 800 mg every 12 hours for 7-14 days with regular food intake and it can be extended if required. At the mentioned dose under fed conditions, satisfactory efficacy against MRSA with a 90%; or higher cumulative fraction of response and probability of target attainment was achieved. Additionally, contezolid also exhibits activity against Mycobacterium tuberculosis and Mycobacterium abscessus.

Skin and soft tissue infections in adolescent chronic myeloid leukemia under dasatinib treatment.

Although skin complications are common adverse events from tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), no reports have focused on skin and soft tissue infections (SSTIs) associated with TKI use. We herein present five episodes of SSTIs in three CML patients under dasatinib treatment. All patients were adolescents and had been receiving dasatinib for more than 4 years. In contrast, none of 41 adult CML patients experienced SSTIs in a retrospective analysis. Our findings suggest that long-term dasatinib treatment in adolescent patients may be associated with the increased risk of SSTIs.

Effectiveness, safety and cost analysis of dalbavancin in clinical practice.

OBJECTIVES: Dalbavancin is approved for the treatment of complicated skin and soft tissue infections. However, there is growing evidence that other gram-positive infections could be treated with this antibiotic. A study was undertaken in a tertiary hospital in Spain to evaluate the effectiveness and safety of dalbavancin in off-label indications and the potential healthcare cost savings. METHODS: A retrospective observational study including all patients treated with dalbavancin in our hospital from October 2016 to August 2019 was carried out. Demographic, clinical and safety variables were collected. Effectiveness was assessed using the clinical and microbiological resolution of the infection and the absence of hospital admissions due to the same infection in the following 3 months. RESULTS: A total of 102 patients were included (69.9% men, n=71; median age 72.5 years (range 56.0-84.0)). Treatment was off label in 71 cases (69.6%). The most frequent off-label indications were catheter-related bacteraemia (15.7%, n=16) and endocarditis (13.6%, n=14). All patients had previously received antibiotics. The main reason for switching to dalbavancin was patient discharge (79.4%, n=81). Dalbavancin was administered during hospitalisation in 66.7% of the patients and in the outpatient setting in 13.7%. The median reduction in length of hospital stay was 14 days per patient. A saving of about 4550 Euros per patient was estimated. 89 patients (93.7%) had clinical and microbiological resolution of the infection at the end of the study. One patient did not finish the dalbavancin infusion due to an allergic reaction. CONCLUSIONS: Our results suggest that dalbavancin is a safe and effective alternative to the off-label treatment of gram-positive infections. Its dosage facilitates early discharge and outpatient management of these patients.

The clinical characteristic and outcome of skin and soft tissue infection in immunosuppressive patients with nephrotic syndrome.

OBJECTIVE: Skin and soft tissue infection (SSTI) is the most common of infectious diseases with high morbidity and mortality. However, the clinical characteristics of SSTI in patients with nephrotic syndrome (NS), especially in those patients who received immunosuppressive therapy, are still lacking. The present study was conducted to investigate the clinical characteristics and outcomes of SSTI in patients with NS. METHODS: A retrospective study was carried out among the patients diagnosed with NS and SSTI, who have priorly received or currently have been receiving immunosuppressive therapy between April 2011 and January 2019; the clinical profile included patient's baseline characteristics, clinical presentation, microbiological findings, treatment, and prognosis. RESULTS: A total of 70 patients were analyzed. Results showed that more than half of the patients were under 35 years old, and moderate infection was the most common type of SSTI. Leg and cellulitis were the most common site of lesion and the typical clinical manifestation of SSTI, respectively. Patients in the severe infection group have a higher level of procalcitonin (PCT) and C-reactive protein (CRP), while a lower level of albumin, CD4+ T and CD8+ T cell count. Moreover, the gram-negative bacteria were the primary pathogens of SSTI in patients with NS, and Klebsiella pneumoniae were the most frequent strains isolated from those patients. Besides, patients in the mild and moderate infection groups experienced a better outcome. CONCLUSIONS: Patients with NS and SSTI usually showed a satisfying outcome with proper anti-infection treatment, but severe SSTI can be life-threatening.

Fournier's gangrene and sodium-glucose co-transporter-2 inhibitors: A meta-analysis of randomized controlled trials.

Fournier's gangrene (FG) is a rare, life-threatening necrotizing fasciitis of the perineum. The US Food and Drug Administration (FDA) released a Drug Safety Communication regarding the risk of FG associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i), relying on the FDA Adverse Event Reporting System. To verify this association, we performed a meta-analysis of all randomized controlled trials enrolling patients with type 2 diabetes, comparing SGLT2i with placebo or different therapies, collecting cases of FG reported as a serious adverse event. Risk of abscess, cellulitis and erysipela were secondary outcomes. We retrieved 84 trials enrolling 42 415 patients in the SGLT2i group and 27 158 patients in comparator groups. No difference was observed between SGLT2i and comparators in the risk of FG (Mantel-Haenzel odds ratio [MH-OR] 0.41 [0.09, 1.82]), abscess (MH-OR 0.94 [0.54, 1.65]), cellulitis (MH-OR 0.90 [0.71, 1.13] or erysipela (MH-OR 0.89 [0.45, 1.77]). The number of events was small, leading to a wide confidence interval that does not allow ruling out an increase in FG or skin and subcutaneous tissue infections.

The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice.

The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48 h before GAS (Group 1), GAS-DS and maintained DS for 48 h (Group 2), DS for 48 h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis.

A systematic review of injecting-related injury and disease among people who inject drugs.

BACKGROUND: Non-viral injecting-related injuries and diseases (IRID), such as abscesses and vascular damage, can result in significant morbidity and mortality if untreated. There has been no systematic assessment of the prevalence of non-viral IRID among people who inject drugs; this review aimed to address this gap, as well as identify risk factors for experience of specific IRID. METHODS: We searched MEDLINE, Embase and CINAHL databases to identify studies on the prevalence of, or risk factors for, IRID directly linked to injecting in samples of people who inject illicit drugs. RESULTS: We included 33 studies: 29 reported IRID prevalence in people who inject drugs, and 17 provided data on IRID risk factors. Skin and soft tissue infections at injecting sites were the most commonly reported IRID, with wide variation in lifetime prevalence (6-69%). Female sex, more frequent injecting, and intramuscular and subcutaneous injecting appear to be associated with skin and soft tissue infections at injecting sites. Cleaning injecting sites was protective against skin infections. Other IRID included infective endocarditis (lifetime prevalence ranging from 0.5-12%); sepsis (2-10%); bone and joint infections (0.5-2%); and thrombosis and emboli (3-27%). CONCLUSIONS: There were significant gaps in the data, including a dearth of research on prevalence of IRID in low- and middle-income countries, and potential risk and protective factors for IRID. A consistent approach to measurement, including standardised definitions of IRID, is required for future research.

[DYNAMICS OF BACTERIOLOGICAL AND PLANIMETRIC INDICES OF THE WOUND UNDER THE ACTION OF THE SILVER NANOPARTICLES, STABILIZED BY MEXIDOL AND POLYVINYLPYRROLIDONE].

Changes in bacteriological indices through the square of the wound of chemical origin under local impact of the silver nanoparticles (NP), stabilized by 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol) and polyvinylpyrrolidone were studied. The wounds of submandibular region were simulated in white rats, using injection of 10% solution of calcium chloride with further opening of necrotic foci and open management of the wound. Beginning from the fifth day, every day the wound was irrigated with liquid, which have contented the stabilized NP of the silver, 0.05% water solution of chlorhexidine or isotonic solution of the the sodium chloride (control). There was established, that the silver NP impact antiseptically and regenerative while the wound treatment, and reduce during 10 days microbial contamination of exudate in 24 times, the wound square--in three times in comparison with original indices. These changes were identical to those while application of chlorhexidine.

Subcutaneous Injection of Percocet: A Case of Severe Soft Tissue Loss.

Prescription drug abuse ranks as the second most common class of illicit drug use in the United States, and one mechanism of opiate abuse involves intravenous injection of enteral narcotics such as oxycodone or hydrocodone. The authors describe a patient who sustained significant soft tissue necrosis after intravenously injecting a solution made from crushed enteral narcotics, with a focus on the operative course that resulted due to a delay in initial definitive treatment. The patient's wounds encompassed 8% total body surface area and covered 247 cm2. A 55-year-old female was admitted to the burn unit (West Penn Burn Center, Western Pennsylvania Hospital, Pittsburgh, PA) after she initially presented with infection and cellulitis to her bilateral upper extremities 3 weeks after intravenously injecting herself with crushed oxycodone/acetaminophen. She underwent numerous sequential operative repairs including initial debridement, placement of dermal replacement templates, and several split-thickness autografts and xenografts. Her total length of stay was 59 days, broken into an initial 47-day stay, and a subsequent 12-day readmission due to graft failure secondary to poor follow-up. As the number of prescription drug abusers rises, it is possible that an increase in attempts to intravenously abuse enteral narcotics may also rise. As such, burn centers should be prepared for the extent of potential limb necrosis and the operative treatment that may ensue.

Fatal necrotizing fasciitis following two suicide attempts with petroleum oil injection.

PURPOSES: Necrotizing fasciitis is an aggressively progressing complication of the skin and soft tissue infections. It has dramatic course and often leads to patient's death. METHODS: In our research, we present the casuistic case concerning double suicide attempt with petroleum oil injection, complicated by the necrotizing fasciitis, patient was with deliberately withheld mental disorders. RESULTS: During the first suicide attempt, the oil substance was injected into the left cubital fossa and left toes areas, what lead to amputation of the upper left limb above the cubitial fossa and the left toes. Afterward, patient gradually recovered and survived. Two years later, another suicide attempt took place with the same substance: a 27-year-old man injected the petroleum oil into the right supraclavicular area. That affected a necrosis penetrating into the mediastinum and the patient died. CONCLUSIONS: To our knowledge, such case of the necrotizing fasciitis has not been previously reported. The mechanism of derivatives of oil influence on tissues is not investigated yet; therefore, treatment method is uncertain and sometimes ineffective.

Severe necrotizing soft-tissue infections and nonsteroidal anti-inflammatory drugs.

BACKGROUND: Severe necrotizing soft-tissue infection (NSTI) is a rare but potentially life-threatening condition if not recognized and treated early. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been implicated as a contributing factor, but their role remains debated. AIMS: The aim of our study was to investigate the potential relationship between cases of NSTI recorded in the French Pharmacovigilance system and exposure to NSAIDs. METHODS: Cases of NSTI and randomly selected matched noncase controls (without skin disease) were identified in the database of the Spontaneous Reporting System in France for the period 2000-2004. Exposure to NSAIDs and other factors were investigated using conditional logistic regression. RESULTS: We found 38 cases of NSTI in 2000-04: 12 infants (0-23 months), 16 children (2-15 years) and 10 adults (>15 years), and we selected 228 controls. The median age of the sample was 4 years. Of the 38 cases, 25 were exposed to ibuprofen and 24 presented with varicella. The adjusted odds ratio for exposure to NSAIDs was 31.38 (95% CI 6.40-153.84), and 17.55 (95% CI 3.47-88.65) for viral infection. Other predisposing factors (diabetes, immunosuppression, injecting drugs) were not found to be associated, although this may have been due to the very small number of cases of NSTI/necrotizing fasciitis in adults reported in the database. CONCLUSION: Despite the limitations related to a spontaneous reporting system, this study indicates a strong association between NSAID use and NSTI. Although it was not possible to conclude if NSAIDs increase the risk of necrotizing complications in all patients, their use may mask the symptoms and delay diagnosis.

Severe upper limb complications from parenteral abuse of Subutex.

INTRODUCTION: Subutex is a sublingual formulation of buprenorphine that is used to treat opioid dependency. It may be abused parenterally with disastrous consequences. CLINICAL PRESENTATION: We present 4 cases of parenteral abuse of Subutex resulting in severe upper limb complications. TREATMENT: Two vascular complications were treated with combinations of anticoagulants, vasodilators, brachial plexus bock and iloprostol. One severe hand abscess required surgical debridement, and 1 median nerve injury required neurolysis. OUTCOME: All patients had a poor outcome. Both patients with vascular complications required multiple amputations, the patient with a thenar abscess had severely impaired thumb function, and the patient with median nerve injury has ongoing neuralgic pain, numbness and thenar weakness. CONCLUSION: The incidence of complications of parenteral abuse of Subutex is increasing in Singapore. These complications have a poor outcome despite adequate management, and are best prevented by education or legal means.

Protean manifestations of intravenous drug use.

Intravenous drug use is an increasing social problem. Repeated venepunctures, injection of insoluble substances and needle sharing habits in intravenous drug users result in complications leading to admissions under various medical specialities. Many of these patients, however, manifest soft tissue wounds requiring specialised care from plastic surgeons. Typical presentations include injection site related abscess, cellulitis, necrotising fasciitis and non-healing wounds. We present a series of 11 consecutive cases treated in our unit over a six-month period, to highlight the varied clinical presentations and potential difficulties in their management.