Factors associated with blood culture positivity in patients with complicated skin and skin structure infection-a population-based study.

Skin and skin structure infection (SSSI) is classified as complicated (cSSSI) if it involves deep subcutaneous tissue or requires surgery. Factors associated with blood culture sampling and bacteremia have not been established in patients with cSSSI. Moreover, the benefit of information acquired from positive blood culture is unknown. The aim of this study was to address these important issues. In this retrospective population-based study from two Nordic cities, a total of 460 patients with cSSSI were included. Blood cultures were drawn from 258 (56.1%) patients and they were positive in 61 (23.6%) of them. Factors found to be associated with more blood culture sampling in multivariate analysis were diabetes, duration of symptoms shorter than 2 days and higher C-reactive protein (CRP) level. Whereas factors associated with less frequent blood culture sampling were peripheral vascular disease and a surgical wound infection. In patients from whom blood cultures were taken, alcohol abuse was the only factor associated with culture positivity, as CRP level was not. Patients with a positive blood culture had antibiotic streamlining more often than non-bacteremic patients. A high rate of blood culture positivity in patients with cSSSI was observed. Factors related to more frequent blood culture sampling were different from those associated with a positive culture.

Mycobacterium nebraskense infection in a dog in Switzerland with disseminated skin lesions.

BACKGROUND: Cutaneous disseminated mycobacteriosis is rare in dogs. To the best of the authors' knowledge, the slowly growing mycobacterial species Mycobacterium nebraskense has not been described before in this species. OBJECTIVE: Description of clinical features, laboratory analyses and treatment regimen of this unusual case. ANIMAL: A 9-year-old female-spayed West Highland white terrier dog presented with progressive nodules and ulcerations on both sides of the thorax and the rostral aspect of the chest. METHODS AND MATERIALS: Investigations involved histopathological examination of skin biopsies (including special stains for fungi, bacteria and mycobacteria), standard and mycobacterial culture (including susceptibility testing), 16S/23S rRNA sequencing and BLAST similarity searching. RESULTS: Ziehl-Neelsen staining of decontaminated biopsy material revealed acid-fast bacteria morphologically consistent with mycobacteria. Treatment with clarithromycin and marbofloxacin achieved partial resolution. A change in the treatment regimen to pradofloxacin and azithromycin resulted in rapid deterioration of skin lesions. Final healing occurred with the addition of prednisolone at an anti-inflammatory dose. The results of mycobacterial culture and susceptibility testing were received 10 and 12 months, respectively, after the first presentation of the dog. Therapy was stopped after 16 months without recurrence of skin lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: This case is noteworthy for the description of a new mycobacterial species contributing to disseminated panniculitis in a dog and for the difficulties experienced in the lengthy empirical treatment of slowly growing nontuberculous mycobacterial infections. The addition of prednisolone to induce complete healing raises the question of whether the mycobacterial infection was primary or whether it occurred secondarily to an ongoing sterile panniculitis.

Retrospective Identification of a Broad IgG Repertoire Differentiating Patients With S. aureus Skin and Soft Tissue Infections From Controls.

Background: Although the relevance of humoral immunity for protection against S. aureus skin and soft tissue infections (SSTIs) has been suggested by several animal and human studies, the question of which human antibodies may be protective has so far impeded the development of a safe and effective vaccine. Because most adults have developed certain anti-S. aureus antibodies due to S. aureus colonization or infection, we hypothesized that the titers of antibodies to S. aureus in uninfected controls would differ from those in infected patients and would also differ in infected patients from the time of acute infection to a 40-day convalescent serum. Methods: To test these hypotheses, we measured human antibody levels against a panel of 134 unique antigens comprising the S. aureus surfome and secretome in subjects with active culture-confirmed S. aureus SSTIs (cases) and in controls with no infection, using a novel S. aureus protein microarray. Results: Most S. aureus SSTI patients (n = 60) and controls (n = 142) had antibodies to many of the tested S. aureus antigens. Univariate analysis showed statistically weak differences in the IgG levels to some antigens in the SSTI patient (case) sera compared with controls. Antibody levels to most tested antigens did not increase comparing acute with 40-day serum. Multiple logistic regression identified a rich subset of antigens that, by their antibody levels, together correctly differentiated all cases from all controls. Conclusions: Antibodies directed against S. aureus antigens were present both in patients with S. aureus SSTIs and in uninfected control patients. We found that SSTI patients and controls could be distinguished only based on differences in antibody levels to many staphylococcal surface and secreted antigens. Our results demonstrate that in the studied population, the levels of anti-S. aureus antibodies appear largely fixed, suggesting that there may be some level of unresponsiveness to natural infection.

Clinical outcome of granulocyte transfusion therapy for the treatment of refractory infection in neutropenic patients with hematological diseases.

Neutropenic patients with hematological diseases are prone to severe infections. Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic approach for these problems. However, the efficacy and complications of GTX have not been well identified. We retrospectively analyzed the clinical outcomes of GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions for 47 patients, 72.3% of these patients' infections were effectively improved, and the overall survival rates at 30 and 120 days were 66.0 and 57.5%, respectively. The patients who experienced neutrophil recovery within 10 days after their therapy initiation had a better response and long-term survival period (14/15, 93.3%, vs 20/32, 62.5%, P = 0.037). Higher-dose granulocytes (> 2.55 × 108/kg) might improve the effective rate of infection in the patients who had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P = 0.049). In addition, GTX benefited the patients who suffered from pulmonary bacterial infections (16/20, 80%) compared with the bloodstream infection group (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data showed that GTX did not affect the incidence of graft-versus-host disease (GVHD) and cytomegalovirus viremia when patients received further HSCT treatment. Collectively, GTX was an adjunct treatment modality for severely neutropenic patients who were likely to experience hematopoietic recovery. More randomized trials are needed to verify the efficacy and complications of GTX therapy.

Factors that affect the duration of antimicrobial therapy for cellulitis.

BACKGROUND: The recommended duration of antibiotic therapy for patients hospitalized with cellulitis is 5-14 days. However, factors that affect the duration of treatment have rarely been examined. METHODS: We conducted an observation study in a regional hospital in Japan to examine factors that affect the duration of antibiotic therapy for cellulitis. Our study included 102 patients with cellulitis of the lower extremities who were treated with intravenous cefazolin alone. Intravenous cefazolin was terminated when redness, swelling, and tenderness of the lower extremities disappeared, and subsequently the patients were discharged. The relationship between the duration (days) of treatment with intravenous cefazolin (DIVC) and clinical factors were analyzed. RESULTS: The median DIVC was 8 days (interquartile range, 7-10 days). On univariate analysis, DIVC correlated significantly with patient age (P = 0.0071) and with C-reactive protein levels before treatment (P = 0.0053). DIVC in patients with diabetes mellitus was significantly longer than that in patients without diabetes mellitus (P = 0.0033). DIVC in patients with blood stream infection was significantly longer than that in patients without blood stream infection (P = 0.029). On multivariate analysis, variables independently associated with longer DIVC included patient age (P = 0.044), C-reactive protein levels before treatment (P = 0.017), presence of diabetes mellitus (P = 0.0021), and presence of blood stream infection (P = 0.028). CONCLUSIONS: Duration of treatment with intravenous antibiotics for cellulitis is associated with patient age, C-reactive protein levels, coexisting diabetes mellitus, and coexisting blood stream infection. These findings should be considered when treatment plans for cellulitis are devised.

[Cutaneous manifestations of Lyme disease : Pitfalls in the serological diagnostic workup]. / Kutane Lyme-Borreliose : Fallstricke der serologischen Diagnostik.

Serology, the detection of B. burgdorferi-specific IgM and IgG serum antibodies, is the most common laboratory test to diagnose cutaneous manifestations of Lyme disease. In a two-tiered approach, an ELISA is used as a screening test. A positive or equivocal ELISA result needs confirmation by a specific immunoblot. The sensitivity of this approach reaches 80-95%. The diagnosis of erythema migrans is based on its typical clinical appearance. Serology is only indicated in atypical cases. In contrast, serology is mandatory in the diagnostic workup of borrelial lymphocytoma and acrodermatitis chronica atrophicans. A positive serology can persist for many years, even after adequate antibiotic treatment. A positive serology is no indication for antibiotic treatment if typical symptoms of Lyme disease are absent.

Evaluation of clinical and serological findings for diagnosis of cutaneous anthrax infection after an outbreak.

PURPOSE: Anthrax, caused by the bacterium Bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. We aimed to evaluate clinical findings and risk factors of patients with cutaneous anthrax infection and report anti-lethal factor (LF) IgG and anti-protective antigen (PA) IgG titers in the serologic diagnosis of disease. METHODS: In this study, serum samples of 18 cutaneous anthrax patients were collected and anti-LF IgG and anti-PA IgG titers were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Twelve (67%) males and 6 (33%) females, with a mean age of 36.06 ± 16.58 years were included in the study. Risk factors identified in the patient population studied were slaughtering (28%), flaying (56%), chopping meat (67%), burying diseased animal corpses (17%) and milking (6%) livestock. Black eschar formation (94%), pruritus (78%) and painful lymphadenopathy (61%) were first three common clinical signs and symptoms, respectively. Fourteen (78%) patients produced a positive IgG response against PA, 11 (61%) patients produced against LF. Three (17%) patients had no response to either antigen. CONCLUSIONS: A detailed history of contact with sick animals or animal products along with clinical findings should be taken at the first step for the diagnosis of cutaneous anthrax infection. Serologic detection of anti-LF IgG and anti-PA IgG with ELISA may be useful auxillary method for establishing the diagnosis.

Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

INTRODUCTION: Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. MATERIALS AND METHODS: Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. RESULTS: The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. CONCLUSIONS: The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

Anti-infective Dosing for Obese Adult Patients: A Focus on Newer Drugs to Treat Methicillin-resistant Staphylococcus aureus Acute Bacterial Skin and Skin Structure Infections.

PURPOSE: Obesity is recognized to be a risk factor for acute bacterial skin and skin structure infections (ABSSSIs) that are associated with methicillin-resistant Staphylococcus aureus (MRSA). Several new antimicrobial agents have been introduced to treat MRSA-related ABSSSI and are dosed with and without regard to weight. This review seeks to explain the pharmacokinetic and pharmacodynamic (PK-PD) rationale for initial and maintenance dosage selection of these newer agents in obese adults. METHODS: A PubMed search was performed using the key words obese or obesity, pharmacokinetics, and the name of each MRSA active drug evaluated in this review. Major themes were identified through a review of this literature. A synopsis of key findings from population PK studies (including reference sources) and independent studies of the PK properties of each new MRSA active agent used to treat ABSSIs were reviewed to derive practical dosing considerations. FINDINGS: Clinical trials of ABSSSIs have increasingly incorporated individuals across a wide body size spectrum. This inclusion of obese adults has been reflected in population PK analyses that have permitted the evaluation of weight and other body size descriptors. In general, the volume of distribution is higher in obese patients, suggesting the need for higher initial (loading) doses if PK bioequivalence is desired. Less certainty exists with selection of a higher maintenance dose, especially for antimicrobial agents with time-dependent PK-PD properties. Selection of higher maintenance doses through alternate scaling approaches in obese patients can be justified on an individual clinical basis. IMPLICATIONS: Maintenance dose modification of several MRSA-targeted anti-infective agents is unlikely to be necessary in obese patients and should be capped if dosed on total weight or this higher dose justified with therapeutic drug monitoring.

In vivo dynamics of active edema and lethal factors during anthrax.

Lethal and edema toxins are critical virulence factors of Bacillus anthracis. However, little is known about their in vivo dynamics of production during anthrax. In this study, we unraveled for the first time the in vivo kinetics of production of the toxin components EF (edema factor) and LF (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice. We stratified the asynchronous infection process into defined stages through bioluminescence imaging (BLI), while exploiting sensitive quantitative methods by measuring the enzymatic activity of LF and EF. LF was produced in high amounts, while EF amounts steadily increased during the infectious process. This led to high LF/EF ratios throughout the infection, with variations between 50 to a few thousands. In the bloodstream, the early detection of active LF and EF despite the absence of bacteria suggests that they may exert long distance effects. Infection with a strain deficient in the protective antigen toxin component enabled to address its role in the diffusion of LF and EF within the host. Our data provide a picture of the in vivo complexity of the infectious process.

[Bloodstream infection due to Campylobacter fetus subspecies fetus and skin involvement: A case series of three patients]. / Bactériémie à Campylobacter fetus subspecies fetus et manifestations cutanées : à propos de trois cas.

INTRODUCTION: Among the species of Campylobacter, C. fetus subspecies fetus is characterized by extra-intestinal manifestations, including bloodstream and cardiovascular infections, occurring preferentially in the context of immunosuppression. The cutaneous lesions are rarely described but may be underestimated. CASE REPORTS: We report on 3 cases of cellulitis with bloodstream infection due to Campylobacter fetus subspecies fetus, without cardiovascular infection in a 72- and 85-year-old women, respectively, and a 79-year-old man. Outcome was successful in all 3 cases after prolonged amoxicillin-clavulanic acid treatment, without relapse. CONCLUSION: C. fetus subspecies fetus is rarely associated with skin and soft tissue infections. Cardiovascular complications may be searched in such context.

Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.

BACKGROUND & OBJECTIVES: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. METHODS: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. RESULTS: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] = 0.9982; slope = 0.9186; intercept = 0.1108). INTERPRETATION & CONCLUSIONS: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

Serum adenosine deaminase activity in cutaneous anthrax.

BACKGROUND: Adenosine deaminase (ADA) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. The aim of this study was to investigate serum ADA activity in patients with cutaneous anthrax. MATERIAL AND METHODS: Sixteen patients with cutaneous anthrax and 17 healthy controls were enrolled. We measured ADA activity; peripheral blood leukocyte, lymphocyte, neutrophil, and monocyte counts; erythrocyte sedimentation rate; and C reactive protein levels. RESULTS: Serum ADA activity was significantly higher in patients with cutaneous anthrax than in the controls (p<0.001). A positive correlation was observed between ADA activity and lymphocyte counts (r=0.589, p=0.021) in the patient group. CONCLUSIONS: This study suggests that serum ADA could be used as a biochemical marker in cutaneous anthrax.

The value of procalcitonin measurement in localized skin and skin structure infection, diabetic foot infections, septic arthritis and osteomyelitis.

Serum procalcitonin (PCT) is an established diagnostic marker for severe or systemic bacterial infections such as pneumonia, sepsis and septic shock. Data regarding the role of PCT in localized infections without systemic inflammatory response syndrome are scarce. The aim of this review is to assess the value of PCT measurements in localized infections such as skin and skin structure infections, diabetic foot infections, septic arthritis (SA) and osteomyelitis. It appears that serum PCT is unlikely to change the clinical practice in skin and skin structure infection. However, serum PCT could have a role in diagnosis and monitoring of diabetic foot infections in hospitalized settings. There are conflicting reports regarding the ability of serum PCT to distinguish SA from non-SA; synovial PCT may be more appropriate in these settings, including in implant-related infections. Better designed studies are needed to evaluate the usefulness of PCT with or without other biomarkers in localized infections.

Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patients with community-acquired bacterial pneumonia (CABP) were used for external model validation. Healthy subjects received 50-2,000 mg ceftaroline fosamil via intravenous (IV) infusion over 1 hour or intramuscular (IM) injection q12h or q24h. ABSSSI and CABP patients received 600 mg of ceftaroline fosamil IV over 1 hour q12h. A three-compartment model with zero-order IV or parallel first-order IM input and first-order elimination described ceftaroline fosamil PK. A two-compartment model with first-order conversion of prodrug to ceftaroline and parallel linear and saturable elimination described ceftaroline PK. Creatinine clearance was the primary determinant of ceftaroline exposure. Good agreement between the observed data and both population (r(2) = 0.93) and individual post-hoc (r(2) = 0.98) predictions suggests the PPK model can adequately approximate ceftaroline PK using covariate information. Such a PPK model can evaluate dose adjustments for patients with renal impairment and generate ceftaroline exposures for use in pharmacokinetic-pharmacodynamic assessments of efficacy in patients with ABSSSI or CABP.

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.

Cutaneous anthrax resulting in renal failure with generalized tissue damage.

Anthrax is a zoonotic infection caused by Bacillus anthracis which can be clinically present in a cutaneous, gastrointestinal or inhalational form depending on the entry site of the agent. The most frequent clinical type with the mildest clinical course is cutaneous anthrax. In this report, a patient with cutaneous anthrax which begins at the dorsal hand and progresses up to the proximal forearm resulting in massive tissue damage is presented. Prerenal azotemia developed due to massive tissue damage and patient was sent to hemodialysis twice.