Effects of salinity on oil dispersant toxicity in the grass shrimp, Palaemonetes pugio.

Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The effects of salinity on the toxicity of two oil dispersants, Corexit® 9500 and Finasol® OSR 52, were examined in this study. Corexit® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5, 20, and 30 ppt. Median acute lethal toxicity thresholds and oxidative stress responses were determined. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Oxidative stress in adult shrimp, as measured by increased lipid peroxidation activity, occurred with exposure to both dispersants. These data will assist environmental managers in making informed decisions regarding dispersant use in future oil spills.

Clinical efficacy of tigecycline used as monotherapy or in combination regimens for complicated infections with documented involvement of multiresistant bacteria.

INTRODUCTION: Tigecycline is an established treatment option for infections with multiresistant bacteria (MRB). It retains activity against many strains with limited susceptibility to other antibiotics. Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospective noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals. MATERIALS AND METHODS: Data on the full population have been published; our present analysis focuses on infections caused by MRB. The study population included patients with complicated infections, high disease severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had comorbidities, including cardiovascular disease, renal insufficiency, and/or diabetes mellitus. Treatment success was defined as cure/improvement without requirement of further antibiotic therapy. RESULTS: Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE) and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB subpopulation, 140 patients received tigecycline monotherapy, 75 were treated with combination regimens. High overall clinical success rates were recorded for MRB infections treated with tigecycline alone (94 %) or in combinations (88 %); in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %), skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100 %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33 %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %). CONCLUSIONS: Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity. These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement.

[Empirical antibiotic therapy in intra-abdomial infections: cases and evidence-based therapeutic recommendations]. / Kalkulierte Antibiotikatherapie bei intraabdominellen Infektionen - Fallbeispiele und evidenzbasierte Therapieempfehlungen.

Intra-abdominal infections (IAI) are a common problem in visceral medicine. In Germany more than 150 000 patients are treated each year for IAI with courses ranging from uncomplicated disease to severe life-threatening manifestations. IAI represent the second most common cause of septic shock and the second most common cause of infection-related mortality in intensive care. Due to increasing antimicrobial resistance, changes in pathogen spectra and increasing patient co-morbidities, recommendations for empirical antibiotic therapy have to be continuously updated: Whereas inadequate empirical treatment is associated with poor prognosis, unselected broad-spectrum therapy may increase antimicrobial resistances. Illustrated by clinical cases of typical intra-abdominal infections, this article reviews recommendations for antibiotic therapy based on national and international guidelines under consideration of local resistance rates and patient-specific factors to provide a basis for improved therapy of this common problem.

[Infection control in the operating room: preventive measures and isolation precautions in cases of multidrug resistant pathogens]. / Infektionskontrolle im OP: Präventions- und Isolierungsmaßnahmen bei multiresistenten Erregern.

BACKGROUND: Providing surgical treatment for patients colonised or infected with multidrug resistant organisms (MDROs) is daily routine in German hospitals. However, there is uncertainty about the application of adequate infection control measures in the OR. One of the reasons is that specific guidelines are not available. MATERIAL AND METHODS: We evaluated current practice in surgical departments of selected German university medical centres using a questionnaire. In addition, centres were asked to provide in-house standard operating procedures (SOP), if available. RESULTS: Nineteen questionnaires from 19 departments within 4 centres and 5 in-house SOPs were ana-lysed. The results showed a broad spectrum of applied infection control measures. Wide variations existed both within centres and within departments of the same centre regardless of existing in-house standards. CONCLUSIONS: Guidelines addressing perioperative infection control measures for patients harbouring MDROs should be developed with a focus on practicability to reduce both transmission of MDROs and unreasonable measures. Implementation of existing SOPs can be a target for optimisation.

[Mucocele of the appendix - a heterogenous surgical pathology]. / Die Mukozele der Appendix - eine inhomogene chirurgische Krankheitsentität.

BACKGROUND: Mucoceles of the appendix are rare. After appendectomy, mucoceles are detected with a frequency of 0.2 to 0.3 %. Both stenosing / obliterating processes and alterations of the epithelium (hyperplasia, mucinous cystadenoma, cystadenoma with uncertain malignant potential (UMP), mucinous cystadenocarcinoma lead to the occurrence of mucoceles. The perforation of a mucocele with possible spread of mucus and cells into the abdominal cavity constitutes a severe complication (pseudomyxoma peritonei). Surgical resection is the curative approach for mucoceles of the appendix. MATERIALS AND METHODS: Data of patients who were treated for an appendiceal mucocele between 1995 and 2009 were analysed retrospectively with regard to clinical presentation, diagnostic measures, surgical procedure and histopathological result. Follow-up was evaluated in telephone interviews. RESULTS: We extracted 5 cases from our database. Clinical symptoms varied greatly among the individual patients, ranging from peracute abdominal pain in the right lower quadrant to chronic obstipation. Results from abdominal ultrasound and / or abdominal CT scans contributed to the indication for surgical intervention in all cases. In 2 patients surgery was stated as urgent whereas in 3 the operation was scheduled electively. In one patient the diagnosis of an appendiceal mucocele was stated preoperatively and in another intraoperatively. In 3 patients only the histopathological result revealed the underlying mucocele. We performed 1 open and 1 laparoscopic appendectomy, 1 open appendectomy with a partial resection of the coecum and 2 laparoscopic ileocoecal resections. One of the patients had a pseudomyxoma peritonei. The histopathological diagnoses ranged from mere epithelial hyperplasia to an adenoma with uncertain malignant potential and a mucinous cystadenocarcinoma. One patient's long-term follow-up could not be evaluated. All other patients had neither recurrence nor any complications after discharge. CONCLUSIONS: Mucoceles of the appendix present with a wide spectrum of clinical symptoms and histopathological alterations. Only an accurate histological analysis reveals the underlying pathological lesion correctly. This study emphasises that a mucocele of the appendix constitutes an important differential diagnosis in patients presenting with pathologies in their right lower abdominal quadrant.

[Fournier's gangrene as special form of necrotizing fasciitis]. / Fournier-Gangrän als Sonderform der nekrotisierenden Fasziitis.

Fournier's gangrene is a special form of necrotizing soft tissue infection (NSTI) and can affect the genital, perineal and perianal regions. Although the disease is named after Fournier, it was first documented by Baurienne in 1764. He described it as idiopathic rapidly progressive gangrene in young otherwise healthy men. Nowadays, the disease is more likely to affect older patients, especially those with pre-existing diseases (e.g. diabetes mellitus and peripheral arterial occlusive disease). Although men are still predominantly affected by Fournier's gangrene, by definition it can also affect women. In most cases it is caused by polymicrobial infections with Enterobacteriaceae. The less common monomicrobial infections are frequently caused by beta hemolyzing Streptococci and then frequently in connection with toxic shock syndrome. Early and aggressive surgical and antimicrobial treatment is crucial to reduce mortality and morbidity. The indications for surgical exploration must be generously considered. The calculated antimicrobial treatment should be carried out as soon as possible, intravenously and in a sufficiently high dosage to catch the expected pathogen. In the era of overspecialization, the treatment of Fournier's gangrene remains a competence that must be comprehensively mastered by clinically active surgeons and urologists. Little has changed with respect to the diagnostic and treatment algorithms in recent years; nevertheless, based on the abovenamed aspects it would appear to be meaningful to present the current aspects and treatment of the disease.

[Necrotizing fasciitis of the extremities and trunk]. / Nekrotisierende Fasziitis der Extremitäten und des Stamms.

Necrotizing fasciitis (NF) is a disease of a group of entities with an aggressive course summarized under the term necrotizing skin and soft-tissue infections (NSTI). It is a life-threatening and often disabling infection and is primarily clinically diagnosed. Initially, clinical signs of infection can be insidious and confounded by absence of fever and typical cutaneous lesions. The later course is characterized by soft tissue lesions, excessive pain and systemic toxicity. As the infection can spread rapidly, and as a delay in treatment is associated with increased mortality, additional diagnostic imaging should be confined to a minimum. Prompt and radical surgical debridement (including repeated debridement after 24 h) is a prerequisite for survival in NF. Also, prompt administration of high-dose broad-spectrum antibiotics and a differentiated intensive treatment are necessary. The role of immunoglobulins and hyperbaric oxygenation remains controversial, therefore, the routine use of these measures cannot be recommended at the moment. Close interdisciplinary collaboration is required in order to optimize the treatment and to save life and limb of patients suffering from this life-threatening infection.

Necrotizing skin and soft-tissue infections in the intensive care unit.

BACKGROUND: Necrotizing skin and soft-tissue infections (NSTI) are rare but potentially life-threatening and disabling infections that often require intensive care unit admission. OBJECTIVES: To review all aspects of care for a critically ill individual with NSTI. SOURCES: Literature search using Medline and Cochrane library, multidisciplinary panel of experts. CONTENT: The initial presentation of a patient with NSTI can be misleading, as features of severe systemic toxicity can obscure sometimes less impressive skin findings. The infection can spread rapidly, and delayed surgery worsens prognosis, hence there is a limited role for additional imaging in the critically ill patient. Also, the utility of clinical scores is contested. Prompt surgery with aggressive debridement of necrotic tissue is required for source control and allows for microbiological sampling. Also, prompt administration of broad-spectrum antimicrobial therapy is warranted, with the addition of clindamycin for its effect on toxin production, both in empirical therapy, and in targeted therapy for monomicrobial group A streptococcal and clostridial NSTI. The role of immunoglobulins and hyperbaric oxygen therapy remains controversial. IMPLICATIONS: Close collaboration between intensive care, surgery, microbiology and infectious diseases, and centralization of care is fundamental in the approach to the severely ill patient with NSTI. As many aspects of management of these rare infections are supported by low-quality data only, multicentre trials are urgently needed.

The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoprotein matrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop.

Double-stranded RNA adenosine deaminase (ADAR1, dsRAD, DRADA) converts adenosines to inosines in double-stranded RNAs. Few candidate substrates for ADAR1 editing are known at this point and it is not known how substrate recognition is achieved. In some cases editing sites are defined by basepaired regions formed between intronic and exonic sequences, suggesting that the enzyme might function cotranscriptionally. We have isolated two variants of Xenopus laevis ADAR1 for which no editing substrates are currently known. We demonstrate that both variants of the enzyme are associated with transcriptionally active chromosome loops suggesting that the enzyme acts cotranscriptionally. The widespread distribution of the protein along the entire chromosome indicates that ADAR1 associates with the RNP matrix in a substrate-independent manner. Inhibition of splicing, another cotranscriptional process, does not affect the chromosomal localization of ADAR1. Furthermore, we can show that the enzyme is dramatically enriched on a special RNA-containing loop that seems transcriptionally silent. Detailed analysis of this loop suggests that it might represent a site of ADAR1 storage or a site where active RNA editing is taking place. Finally, mutational analysis of ADAR1 demonstrates that a putative Z-DNA binding domain present in ADAR1 is not required for chromosomal targeting of the protein.

Xlrbpa, a double-stranded RNA-binding protein associated with ribosomes and heterogeneous nuclear RNPs.

We have cloned and characterized Xlrbpa, a double-stranded RNA-binding protein from Xenopus laevis. Xlrbpa is a protein of 33 kD and contains three tandemly arranged, double-stranded RNA-binding domains (dsRBDs) that bind exclusively to double-stranded RNA in vitro, but fail to bind either single-stranded RNA or DNA. Sequence data and the overall organization of the protein suggest that Xlrbpa is the Xenopus homologue of human TAR-RNA binding protein (TRBP), a protein isolated by its ability to bind to human immunodeficiency virus (HIV) TAR-RNA. In transfection assays, TRBP has also been shown to inhibit the interferon-induced protein kinase PKR possibly by direct physical interaction. To determine the function of Xlrbpa and its human homologue we studied the expression and intracellular distribution of the two proteins. Xlrbpa is ubiquitously expressed with marked quantitative differences amongst all tissues. Xlrbpa and human TRBP can be detected in the cytoplasm and nucleus by immunofluorescence staining and Western blotting. Sedimentation gradient analyses and immunoprecipitation experiments suggest an association of cytoplasmic Xlrbpa with ribosomes. In contrast, a control construct containing two dsRBDs fails to associate with ribosomes in microinjected Xenopus oocytes. Nuclear staining of Xenopus lampbrush chromosome preparations showed the association of the protein with nucleoli, again indicating an association of the protein with ribosomal RNAs. Additionally, Xlrbpa could be located on lampbrush chromosomes and in snurposomes. Immunoprecipitations of nuclear extracts demonstrated the presence of the protein in heterogeneous nuclear (hn) RNP particles, but not in small nuclear RNPs, explaining the chromosomal localization of the protein. It thus appears that Xlrbpa is a general double-stranded RNA-binding protein which is associated with the majority of cellular RNAs, ribosomal RNAs, and hnRNAs either alone or as part of an hnRNP complex.

Brominating oxidants generated by human eosinophils.

Eosinophils are white blood cells that in humans are found in association with helminthic infections and various inflammatory disease processes. These cells contain a unique lysosomal peroxidase that oxidizes halides to generate highly reactive and toxic hypohalous acids. Although chloride is found in vivo at concentrations at least 1000-fold greater than those of other halides, human eosinophils did not preferentially oxidize chloride under physiologic conditions. Instead, eosinophils used bromide, a halide with a hitherto unknown function in humans, to generate a halogenating oxidant with characteristics similar, if not identical, to those of hypobromous acid. These results indicate that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.

Diffuse postoperative peritonitis -- value of diagnostic parameters and impact of early indication for relaparotomy.

OBJECTIVE: Current criteria for performing relaparotomy for suspected peritonitis are non explicit and based on non-quantitative, subjective arguments or hospital practice. The aim of this study was to determine the value of routinely used clinical and diagnostic parameters in early detection of postoperative, diffuse peritonitis (PP). Furthermore, the prognosis and outcome after early indication for relaparotomy in patients with PP compared to community-aquired peritonitis (CAP) was evaluated. METHODS: Between 1999 and 2008, a total of 251 patients with diffuse secondary peritonitis either postoperative (PP) or community acquired (CAP) were analyzed retrospectively. PP (n = 114) and CAP (n = 137) were compared regarding physical examination, MPI-Score, APACHE II-Score, evidence of organ failure, laboratory parameters, diagnostic instruments and clinical course. The treatment regimen comprised surgical source control (with/without programmed lavage), abdominal closure and relaparotomy on demand, broad spectrum antibiotic therapy and intensive care support. RESULTS: The APACHE II-Score (20 CAP vs. 22 PP, p = 0.012), MPI-Score (27 CAP vs. 30 PP, p = 0.001) and the number of lavages differed significantly. Positive phyiscal testing and signs of sepsis (abdominal pain (81.6% PP vs. CAP 97.1%, p = 0.03), rebound tenderness (21.9% vs. 35.8%, p = 0.02), fever (35.1% vs. 51.8%, p = 0.03)) occurred significantly less often in the PP patients than in the CAP group. Conventional radiography (66.2%) and ultrasonography (44.3%) had a lower diagnostic sensitivity than did abdominal CT-scan (97.2%). Mortality was higher in the PP group but did not differ significantly between the two groups (47.4% PP vs. 35.8% CAP, p = 0.06). CONCLUSION: The value of physical tests and laboratory parameters in diagnosing abdominal sepsis is limited. CT-scanning revealed the highest diagnostic accuracy. A treatment regimen of early relaprotomy appears to be the most reasonable strategy for as early discovery of postoperative peritonitis as possible.

[Multidrug resistant gram-negative bacteria : Clinical management pathway for patients undergoing elective interventions in visceral surgery]. / Multiresistente gramnegative Bakterien : Klinischer Managementpfad für Patienten mit elektiven Eingriffen in der Viszeralchirurgie.

BACKGROUND: Only a few antibiotics are available for treatment of infections with multidrug resistant gram-negative bacteria (MRGN). The management of patients with MRGN colonization or infection is therefore of great importance with respect to postoperative morbidity and mortality. OBJECTIVE: This article presents a description of the management pathway for patients with MRGN colonization. RESULTS: The prevalence of MRGN colonization is increasing, particularly for persons with contact to the healthcare system in endemic regions. The Robert Koch Institute demands an obligatory MRGN screening and isolation of patients with geographic or contact-related exposure risk for colonization with 4MRGN (carbapenemase producers). For patients with elective visceral interventions a prompt sensitive screening before inpatient admission is wise. Strict basic hygiene measures are essential to prevent transmission. Isolation is indicated for patients with 4MRGN and also for patients with 3MRGN in risk areas. Risk patients with unknown status are preemptively isolated. Perioperative antibiotic prophylaxis should be administered as a single dose and in cases of MRGN colonization substances effective against MRGN should be given if necessary. For treatment of secondary/tertiary peritonitis with a risk of MRGN involvement and in hemodynamically instable patients, effective extended spectrum beta-lactamase (ESBL) substances should primarily be used (e.g. tigecycline, carbapenems, ceftolozane/tazobactam and ceftazidim/avibactam). Ceftazidim/avibactam is also a novel therapy option for infections with carbapenamase-producing enterobacteria. CONCLUSION: The structured implementation of MRGN screening in patients at risk, stringent basic hygiene, targeted isolation and adequate calculated antibiotic therapy are essential measures in the management of the problem of MRGN in visceral surgery.

The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear localization signal and displays the characteristics of a shuttling protein.

The RNA-editing enzyme ADAR1 (adenosine deaminase that acts on RNA) is a bona fide nuclear enzyme that has been cloned from several vertebrate species. Putative nuclear localization signals (NLSs) have been identified in the aminoterminal regions of both human and Xenopus ADAR1. Here we show that neither of these predicted NLSs is biologically active. Instead, we could identify a short basic region located upstream of the RNA-binding domains of Xenopus ADAR1 to be necessary and sufficient for nuclear import. In contrast, the homologous region in human ADAR1 does not display NLS activity. Instead, we could map an NLS in human ADAR1 that overlaps with its third double-stranded RNA-binding domain. Interestingly, the NLS activity displayed by this double-stranded RNA-binding domain does not depend on RNA binding, therefore showing a dual function for this domain. Furthermore, nuclear accumulation of human (hs) ADAR1 is transcription dependent and can be stimulated by LMB, an inhibitor of Crm1-dependent nuclear export, indicating that hsADAR1 can move between the nucleus and cytoplasm. Regulated nuclear import and export of hsADAR1 can provide an excellent mechanism to control nuclear concentration of this editing enzyme thereby preventing hyperediting of structured nuclear RNAs.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

[Antibiotic therapy of intra-abdominal infections in the era of multiresistance]. / Antibiotikatherapie intraabdomineller Infektionen im Zeitalter der Multiresistenz.

Recommendations for the treatment of intra-abdominal infections (IAI) caused by drug-resistant bacteria often fail to mention the bacteria of concern (e.g. vancomycin-resistant enterococci, extended spectrum beta-lactamase-producing (ESBL) Enterobacteriaceae, multi-drug resistant Pseudomonas spp., carbapenem-resistant organisms and Acinetobacter spp.) and all available drugs. The group of patients suffering from IAI due to resistant bacteria includes the entire group of postoperative and tertiary peritonitis and necrotizing pancreatitis. This article provides information for the management of a very important group of diseases with a substantial morbidity and mortality. An individual patient-centered approach is mandatory to evaluate the optimal antimicrobial treatment regimen. Especially in gram-negative bacteria, which are the predominant cause only a few options remain for treatment. Clinical data with a high level of evidence are very limited. Future studies should focus on pharmacokinetic and pharmakodynamic aspects in critically ill patients, in the sense of antibiotic stewardship in order to elucidate the real life efficacy and safety of antibiotics for the treatment of life-threatening IAI.

[Characteristics of postoperative peritonitis]. / Besonderheiten der postoperativen Peritonitis.

Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

Therapeutic management of peritonitis: a comprehensive guide for intensivists.

PURPOSE: The management of peritonitis in critically ill patients is becoming increasingly complex due to their changing characteristics and the growing prevalence of multidrug-resistant (MDR) bacteria. METHODS: A multidisciplinary panel summarizes the latest advances in the therapeutic management of these critically ill patients. RESULTS: Appendicitis, cholecystitis and bowel perforation represent the majority of all community-acquired infections, while most cases of healthcare-associated infections occur following suture leaks and/or bowel perforation. The micro-organisms involved include a spectrum of Gram-positive and Gram-negative bacteria, as well as anaerobes and fungi. Healthcare-associated infections are associated with an increased likelihood of MDR pathogens. The key elements for success are early and optimal source control and adequate surgery and appropriate antibiotic therapy. Drainage, debridement, abdominal cleansing, irrigation, and control of the source of contamination are the major steps to ensure source control. In life-threatening situations, a "damage control" approach is the safest way to gain time and achieve stability. The initial empirical antiinfective therapy should be prescribed rapidly and must target all of the micro-organisms likely to be involved, including MDR bacteria and fungi, on the basis of the suspected risk factors. Dosage adjustment needs to be based on pharmacokinetic parameters. Supportive care includes pain management, optimization of ventilation, haemodynamic and fluid monitoring, improvement of renal function, nutrition and anticoagulation. CONCLUSIONS: The majority of patients with peritonitis develop complications, including worsening of pre-existing organ dysfunction, surgical complications and healthcare-associated infections. The probability of postoperative complications must be taken into account in the decision-making process prior to surgery.

Weight-based antibiotic dosing in a real-world European study of complicated skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.

We aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs.

Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections.

Diabetes mellitus affects 284 million adults worldwide and is increasing in prevalence. Accelerated atherosclerosis in patients with diabetes mellitus contributes an increased risk of developing cardiovascular diseases including peripheral vascular disease (PVD). Immune dysfunction, diabetic neuropathy and poor circulation in patients with diabetes mellitus, especially those with PVD, place these patients at high risk for many types of typical and atypical infections. Complicated skin and soft-tissue infections (cSSTIs) are of particular concern because skin breakdown in patients with advanced diabetes mellitus and PVD provides a portal of entry for bacteria. Patients with diabetes mellitus are more likely to be hospitalized with cSSTIs and to experience related complications than patients without diabetes mellitus. Patients with PVD requiring lower extremity bypass are also at high risk of surgical site and graft infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent causative pathogen in cSSTIs, and may be a significant contributor to surgical site infections, especially in patients who are colonized with MRSA on hospital admission. Patients with cSSTIs and diabetes mellitus or PVD experience lower clinical success rates than patients without these comorbidities, and may also have a longer length of hospital stay and higher risk of adverse drug events. Clinicians should be vigilant in recognizing the potential for infection with multi-drug-resistant organisms, especially MRSA, in these populations and initiating therapy with appropriate antibiotics.