Skin and subcutaneous infections

People who inject drugs (PWID) are at increased risk for numerous negative health outcomes. Subcutaneous injections (aka skin popping) can result in greater risk of skin and soft tissue infections (SSTIs), but less is known about PWID who choose this route of administration. This study compares subcutaneous injectors to intravenous injectors, characterizes those who inject subcutaneously, and examines whether subcutaneous injection is associated with SSTIs in the past year. A cohort of hospitalized PWID (n = 252) were interviewed regarding injection-related behaviors, history of SSTI, and knowledge of subcutaneous injection risk. We examined differences between those who do and do not inject subcutaneously and used a negative binomial regression model to estimate adjusted odds associating subcutaneous injection and SSTI. Participants averaged 38 years, with 58.3% male, 59.5% White, 20.6% Black, and 15.9% Latinx. PWID who performed subcutaneous injection were not demographically different from other PWID; however, the mean rate of past year SSTIs was higher for persons injecting subcutaneously than for those who did not (1.98 vs 0.96, P < 0.001). Persons injecting subcutaneously did not differ from those who injected intravenously in terms of their knowledge of subcutaneous injection risk (P = 0.112) and knowledge score was not associated with SSTIs (P = 0.457). PWID who perform subcutaneous injections are demographically similar to other PWID but had higher rates of past year SSTIs. Knowledge of subcutaneous injection risk was not associated with SSTI risk.

Mapping the infectious burden in VEXAS syndrome: a systematic review and rationale for prevention.

Nontuberculous mycobacteria (NTM) are a group of organisms widely existing in the environment, which can cause infections of various organs and tissues in human body. Because of the aging of population, the development of cosmetics and transplant operations, as well as the increase in HIV infection, the incidence of cutaneous NTM infection keeps increasing these years, and reports of small-scale outbreaks are not uncommon. Due to the atypical clinical and pathological manifestations as well as the limitations of the detection capabilities of medical institutions, cutaneous NTM infection is easily misdiagnosed or missed diagnosed. In addition, the antimicrobial susceptibility of NTM is quite different and some strains can easily develop resistance to antibiotics, regimens usually require multiple antibiotics for extended periods of time, however, the results are often complicated by side effects and drug interactions. With the development of research in recent years, people have gained a new understanding of the diagnosis and treatment of cutaneous NTM infection. New progress has been made in the research of treatment methods, drugs, phage therapy, vaccines and so on. This article reviews the progress of diagnosis and treatment of cutaneous NTM infection. 摘要 ：非结核分枝杆菌(nontuberculous mycobacteria, NTM)是一类广泛存在于各种环境中的微生物, 可引起人体 多种器官和组织的感染。由于人口老龄化 , 美容、移植手术的广泛开展以及HIV感染的增加, 近年来皮肤NTM病的发 生率一直呈逐渐升高的趋势, 小范围内爆发的报道也不少。由于临床和病理表现多不典型以及医疗机构检测能力的 限制, 皮肤NTM病极易被漏诊和误诊。同时各种NTM对药物敏感性差异很大、部分菌种极易对抗生素产生耐药, 需联 合多种抗生素长疗程治疗, 但药物之间的相互作用及副作用使治疗效果往往不尽如人意。随着近年来研究的深人, 人 们对于皮肤NTM病的诊断和治疗等方面有了新的认识, 在治疗手段、新型药物、噬菌体疗法、疫苗等领域的研究都有了 新的进展。本文对皮肤NTM病诊断和治疗等方面的进展进行了综述。

Control of Pseudomonas aeruginosa Skin Infections in Mice Is Mast Cell-Dependent

Moderate-to-severe atopic dermatitis (AD) is associated with an increased frequency of infections which can lead to hospitalizations. Some treatments used for moderate-to-severe AD can be associated with an increased risk of infection, contributing to a limitation of their long-term use. Dupilumab is a biologic agent that targets the shared signalling pathway for interleukin (IL)-4 and IL-13 and has not been associated with increased risk of overall skin infection rates in clinical trials. To report rates of infection in patients with AD across age groups treated with dupilumab, with a special focus on non-herpetic skin and herpetic infections. We analysed exposure-adjusted infection rates (number of patients per 100 patient-years, nP/100PY) during the study treatment periods for MedDRA terms under the System Organ Class Infections and Infestations (overall infections), including adjudicated skin infections (excluding herpetic infections) and High-Level Term Herpes Virus Infections. Patients with moderate-to-severe AD enrolled in phase 2 (adults) or phase 3 clinical studies received various regimens. Young children (aged 6 months to 5 years, NCT03346434 part B) received dupilumab 200/300 mg (n = 83) every 4 weeks (q4w) or placebo (n = 78) with topical corticosteroids (TCS). Children (aged 6–11 years, NCT03345914) received dupilumab 300 mg q4w (n = 120), or 100/200 mg q2w (n = 122), or placebo (n = 120) with TCS. Adolescents (aged 12–17 years, NCT03054428) received dupilumab 300 q4w (n = 83), or 200/300 mg q2w (n = 82), or placebo (n = 85). Adults (NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986 and NCT02755649) received dupilumab 300 mg q2w (n = 746), or 300 mg qw (n = 1095), or placebo (n = 1091). Rates for dupilumab doses are provided in the order specified above. Post-hoc nominal P-values are between dupilumab and placebo. The rate of overall infections (nP/100PY) in the dupilumab treatment groups was numerically lower than in the placebo group in young children (placebo: 246; dupilumab: 185) and in children (placebo: 244; dupilumab: 184, 171) and similar between groups in adolescents (placebo: 204; dupilumab: 210, 181), and in adults (placebo: 129; dupilumab: 134, 126). Adjudicated non-herpetic skin infection rates (nP/100PY) were significantly lower in most dupilumab-treated groups compared with placebo in young children (placebo: 93; dupilumab: 43 [P &amp;lt; 0.05]), children (placebo: 48; dupilumab: 20 [P &amp;lt; 0.05], 28 [n.s.]), and adults (placebo: 27; dupilumab: 16 [P &amp;lt; 0.01], 14 [P &amp;lt; 0.0001]) and numerically lower in adolescents (placebo: 70; dupilumab: 34, 34). Overall herpes infection rates (nP/100PY) in dupilumab treatment groups were similar compared with placebo in young children (placebo: 17; dupilumab: 20), children (placebo: 17; dupilumab: 5, 11), adolescents (placebo: 12; dupilumab: 16, 4) and adults (placebo: 10; dupilumab: 15, 11). Infection rates (nP/100PY) of clinically important herpetic infections, eczema herpeticum and herpes zoster, were numerically lower in dupilumab-treated young children (placebo: 4; dupilumab: 0), adolescents (placebo: 4; dupilumab: 0, 0), and adults (placebo: 4; dupilumab: 2 [n.s.], 1 [P &amp;lt; 0.01]), and numerically higher in children (placebo: 0; dupilumab: 3, 3). Dupilumab treatment in children as young as 6 months of age, and in adolescents and adults with atopic dermatitis is generally associated with lower rates of non-herpetic skin infections compared with placebo and did not increase the risk of overall infections in these data sets.

Introduction:Mycobacterium haemophilum is one of the non-tuberculous mycobacteria (NTM) that can cause cutaneous infection. As acid-fast staining cannot distinguish NTM from Mycobacterium tuberculosis, and as skin culture for M. haemophilum is not performed routinely, the diagnosis of M. haemophilum infection in Thailand is rarely made.Case presentation:Between 2006 and 2009, five patients with M. haemophilum infection were diagnosed in Ramathibodi Hospital, a tertiary care centre in Bangkok, Thailand. The patients were aged 3, 29, 47, 75 and 76 years, and four were immunocompromised. Three patients received immunosuppressive medication. Most patients presented with subacute cutaneous infection. A suboptimal response to conventional antibiotics raised suspicions of M. haemophilum cutaneous infections, which can occur in immunocompromised patients. Diagnoses of these cases were made by skin culture for mycobacteria at an incubating temperature of around 30 °C with iron supplementation, DNA sequencing, or PCR/restriction enzyme analysis. Rifampicin, ofloxacin and clarithromycin were active against all isolates, whereas ethambutol and streptomycin were inactive.Conclusion:Skin culture should be performed under special conditions or molecular technique should be used to identify M. haemophilum in susceptible patients.

Bacterial skin and soft tissues infections (SSTI) often determine acute disease and frequent emergency recovering, and they are one of the most common causes of infection among groups of different ages. Given the variable presentation of SSTI, a thorough assessment of their incidence and prevalence is difficult. The presence of patient-related (local or systemic) or environmental risk factors, along with the emergence of multi-drug resistant pathogens, can promote SSTI. These infections may present with a wide spectrum of clinical features and different severity, and can be classified according to various criteria. Many bacterial species can cause SSTI, but Gram-positive bacteria are the most frequently isolated, with a predominance of Staphylococcus aureus and Streptococcus pyogenes. The diagnosis of SSTI requires an extended clinical history, a thorough physical examination and a high index of suspicion. Early diagnosis is particularly important in complicated infections, which often require laboratory studies, diagnostic imaging and surgical exploration. SSTI management should conform to the epidemiology, the aetiology, the severity and the depth of the infection. Topical, oral or systemic antimicrobial therapy and drainage or debridement could be necessary, along with treatment of a significant underlying disease. This review discusses the epidemiology, the pathogenesis and the classification of bacterial SSTI, describes their associated risk factors and their clinical presentations. The authors provide a rational diagnostic and therapeutic approach to SSTI in respect of antibiotic resistance and currently available antimicrobial agents.

The protein product of varicella-zoster virus (VZV) ORF47 is a serine/threonine protein kinase and tegument component. Evaluation of two recombinants of the Oka strain, rOka47DeltaC, with a C-terminal truncation of ORF47, and rOka47D-N, with a point mutation in the conserved kinase motif, showed that ORF47 kinase function was necessary for optimal VZV replication in human skin xenografts in SCID mice but not in cultured cells. We now demonstrate that rOka47DeltaC and rOka47D-N mutants do not infect human T-cell xenografts. Differences in the growth of kinase-defective ORF47 mutants allowed an examination of requirements for VZV pathogenesis in skin and T cells in vivo. Although virion assembly was reduced and no virion transport to cell surfaces was observed, epidermal cell fusion persisted, and VZV polykaryocytes were generated by rOka47DeltaC and rOka47D-N in skin. Virion assembly was also impaired in vitro, but VZV-induced cell fusion continued to cause syncytia in cultured cells infected with rOka47DeltaC or rOka47D-N. Intracellular trafficking of envelope glycoprotein E and the ORF47 and IE62 proteins, components of the tegument, was aberrant without ORF47 kinase activity. In summary, normal VZV virion assembly appears to require ORF47 kinase function. Cell fusion was induced by ORF47 mutants in skin, and cell-cell spread occurred even though virion formation was deficient. VZV-infected T cells do not undergo cell fusion, and impaired virion assembly by ORF47 mutants was associated with a complete elimination of T-cell infectivity. These observations suggest a differential requirement for cell fusion and virion formation in the pathogenesis of VZV infection in skin and T cells.

Objective To investigate the clinical features, treatment effect and prognosis of Herpes Zoster(HZ) among patients with acquired immunodeficiency syndrome (AIDS). Methods Clinical data of 72 AIDS-HZ patients in our hospital were retrospectively reviewed, then the data including clinical characteristics, laboratory examination, treatment and the prognosis of patients were statistically analyzed. Results Our study showed that the majority of these patients were male (65.28%) and Uyghur (79.17%), with a mean age of 37.22±8.26 years. 39(54.17%)patients have a history of intravenous drug using (IDUs). The rash was common seen in the trunk (68.06%) and limbs (26.39%), two or more than two were seen in 12 patients (16.67%). 21(29.17%) were combined by skin infections and 67 patients (93.06%) complained with pain. Forty seven(65.28%) patients had a lower CD4+ T lymphocyte counts (<350 cells/ μl). The cure rate was 75% (54/72) and the effective rate was 100% after standard treatment (including antiretroviral therapy, drugs and analgesia therapy). Conclusions HIV/AIDS-HZ is common in male Uygur patients in Xinjiang. More than half of the cases are IDUs and have a lower CD4 count (<350 cells/ μl). Herpes zoster may occurred as a manifestation of immune reconstitution after HAART. However, most of patients with HIV/AIDS-HZ case had a good prognosis after standard treatment. Key words: HIV; AIDS; Herpes zoster; Clinical features

Background. Skin and soft tissue infections (SSTIs) in cancer patients represent a diagnostic challenge, as etiologic diagnosis is often missing, and clinical assessment of severity is difficult. Few studies have described (SSTIs) in patients with solid tumours (STs). Patients and Methods. Records of patients with ST and SSTI, cared for at the University Hospital of Heraklion, from 2002 to 2006 were retrospectively studied. Results. A total of 81 episodes of SSTIs, occurring in 71 patients with ST, have been evaluated. Their median age was 65 years (34–82). The most common underlying malignancy was breast cancer in 17 patients (24%). Most episodes (89%) occurred in nonneutropenics. Cellulitis/erysipelas was the most common clinical presentation (56; 69%). Bacterial cultures were possible in 29 (36%) patients. All patients received antimicrobial therapy, while in 17 episodes (21%) an incision and drainage was required. Treatment failure occurred in 20 episodes (25%). Five patients (7%) died due to sepsis. None was neutropenic. Severe sepsis on admission (P = 0.002) and prior blood transfusion (P = 0.043) were independent predictors of treatment failure. Conclusion. SSTIs can be life threatening among patients with ST. Early diagnosis and appropriate treatment are of the utmost importance, since sepsis was proven a significant factor of unfavourable outcome.

Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella upon primary infection and zoster upon reactivation from latency in sensory ganglion neurons. The replication of herpesviruses requires manipulation of cell signaling pathways. Notably, CREB, a factor involved in the regulation of several cellular processes, is activated upon infection of T cells with VZV. Here, we report that VZV infection also induced CREB phosphorylation in fibroblasts and that XX-650-23, a newly identified inhibitor of the phosphorylated-CREB (pCREB) interaction with p300/CBP, restricted cell-cell spread of VZV in vitro CREB phosphorylation did not require the viral open reading frame 47 (ORF47) and ORF66 kinases encoded by VZV. Evaluating the biological relevance of these observations during VZV infection of human skin xenografts in the SCID mouse model of VZV pathogenesis showed both that pCREB was upregulated in infected skin and that treatment with XX-650-23 reduced infectious-virus production and limited lesion formation compared to treatment with a vehicle control. Thus, processes of CREB activation and p300/CBP binding are important for VZV skin infection and may be targeted for antiviral drug development. Varicella-zoster virus (VZV) is a common pathogen that causes chicken pox and shingles. As with all herpesviruses, the infection is acquired for life, and the virus can periodically reactivate from latency. Although VZV infection is usually benign with few or no deleterious consequences, infection can be life threatening in immunocompromised patients. Otherwise healthy elderly individuals who develop zoster as a consequence of viral reactivation are at risk for postherpetic neuralgia (PHN), a painful and long-lasting complication. Current vaccines use a live attenuated virus that is usually safe but cannot be given to many immunodeficient patients and retains the capacity to establish latency and reactivate, causing zoster. Antiviral drugs are effective against severe VZV infections but have little impact on PHN. A better understanding of virus-host cell interactions is relevant for developing improved therapies to safely interfere with cellular processes that are crucial for VZV pathogenesis.

Paecilomycosis Lilacinus Infection of the Immunocompromised Host

BackgroundThe role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients.We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples.MethodsWe collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC.ResultsPapillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV.ConclusionsOur results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.

Cytomegalovirus-induced cutaneous vasculopathy and perianal ulceration

BackgroundMycobacterium fortuitum complex is a group of rapidly growing nontuberculous mycobacteria (NTM) associated with skin and soft-tissue infections after surgery or trauma. Treatment of NTM is challenging, due to resistance to multiple antimycobacterial agents. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP-synthase. The drug has recently been approved for the treatment of multidrug-resistant tuberculosis and evidence of its in vitro efficacy against NTM, including Mycobacterium fortuitum complex, has been published.Case presentationA 20-year-old Caucasian woman with chronic skin and soft tissue infection in the lower leg following a traffic accident in Vietnam underwent a tedious journey of healthcare visits, hospital admissions, empiric antimicrobial treatments, surgical debridement and plastic reconstruction before definite diagnosis of Mycobacterium fortuitum complex-infection was established by culture from a tissue biopsy and targeted antimycobacterial therapy was administered. Histopathological examination revealed granulomatous purulent inflammation, which strongly supported the diagnosis. Genotypic identification was performed and broth microdilution for susceptibility testing showed macrolide resistance. Five weeks of induction treatment with intravenous amikacin, imipenem / cilastin, and oral levofloxacin was administered, followed by all-oral treatment with bedaquiline combined with levofloxacin for four months, which was well-tolerated and led to persistent healing with scars but without signs of residual infection.ConclusionsBedaquiline is a promising novel agent for NTM treatment, although clinical data are limited and trials evaluating efficacy, safety, and resistance of bedaquiline are required. To our knowledge, this is the first reported case of successful in vivo use of bedaquiline for a skin and soft tissue infection caused by Mycobacterium fortuitum complex.