Necrotizing Fasciitis Within 72 hours After Presentation with Skin and Skin Structure Infection.

INTRODUCTION: A small percentage of patients with skin infections later develop necrotizing fasciitis (NF). Diagnostic testing is needed to identify patients with skin infections at low risk of NF who could be discharged from the emergency department (ED) after antibiotic initiation. Elevated lactate has been associated with NF; existing estimates of the frequency of NF are based on retrospective reviews, and cases often lack testing for lactate. We present the incidence of patients with skin infections who developed NF and their baseline lactates. METHODS: In four phase-3 trials, 2883 adults with complicated or acute bacterial skin and skin structure infections were randomized to dalbavancin or comparator, with early and late follow-up visits through Day 28. We prospectively collected baseline plasma lactates in one trial to assess an association with NF. RESULTS: NF was diagnosed in 3/2883 patients (0.1%); all three survived. In the study with prospectively collected baseline lactates (n = 622), 15/622 (2.4%) had a lactate ≥4 millimoles per liter (mmol/L), including 3/622 (0.5%) with a lactate ≥7 mmol/L. NF was not seen in patients with a lactate <4 mmol/L; NF was seen in 1/15 (6.7%) with a lactate ≥4 mmol/L, including 1/3 (33.3%) with lactate ≥7 mmol/L. CONCLUSIONS: NF incidence within 72 hours of antibiotic initiation in patients with complicated or acute bacterial skin and skin structure infections was extremely low (0.1%) and occurred in 6.7% with a lactate ≥4 mmol/L. Lactate <4 mmol/L can be used to identify patients at low risk of NF who could be safely discharged from the ED after antibiotic initiation.

Is lymphatic reconstitution possible after meshed skin grafting?

Restorative potential of lymph transport after skin graft has rarely been discussed. We report a case of lymphatic reconstitution across meshed, split-thickness skin graft performed for a patient with necrotizing fasciitis. The patient underwent extensive circumferential soft tissue debridement of the lower leg and resurfacing of the skin defect with meshed split-thickness skin graft. Indocyanine green fluorescence lymphography was performed 3 years after surgery and demonstrated that injected dye in the foot traveled across the skin graft and reached to the adjacent native skin in the proximal region. Our observation revealed that transferred split-thickness skin graft possessed some potential to allow for transport of lymph fluid possibly owing to the retention of lymphatic capillaries.

Antibacterial gauzes are effective in preventing infections after percutaneous endoscopic gastrostomy placement: a retrospective analysis.

OBJECTIVES: The most common complication after percutaneous endoscopic gastrostomy (PEG) placement is peristomal wound infection (up to 40% without antibiotic prophylaxis). Single-dose parenteral prophylactic antibiotics as advised by current guidelines decrease the infection rate to 9-15%. We assume a prolonged effect of local antibiotic treatment with antibacterial gauzes. This study is the first to describe the effect of antibacterial gauzes in preventing infections in PEG without the use of antibiotics. METHODS: A retrospective data analysis was carried out of all patients with PEG insertion between January 2009 and October 2014 in the Catharina Hospital Eindhoven. Data include placement and the period of the first 2 weeks after PEG placement, and long-term follow-up. All patients received a locally applied antibacterial gauze polyhexamethylene biguanide immediately following PEG insertion for 3 days. No other antibiotics were administered. The main outcomes were wound infection, peritonitis, and necrotizing fasciitis; secondary outcomes included other complications. RESULTS: A total of 331 patients with only antibacterial gauzes were analyzed. The total number of infections 2 weeks after PEG insertion was 9.4%, including 8.2% minor and 1.2% major infections (peritonitis). No wound infection-related mortality or bacterial resistance was found. Costs are five times lower than antibiotics, and gauzes are more practical and patient friendly for use. CONCLUSION: Retrospectively, antibacterial gauzes are at least comparable with literature data on parenteral antibiotics in preventing peristomal wound infection after PEG placement, with an infection rate of 9.4%. Rates of other complications found in this study were comparable with current literature data.

Prevention and management of cesarean wound infection.

Cesarean wound infections represent a significant health and economic burden. Several modifiable risk factors have been identified for their development. Understanding these risks and techniques to manage cesarean wounds is essential for providers. In this article, these factors and prophylactic and therapeutic interventions are reviewed.

TDM-guided therapy with daptomycin and meropenem in a morbidly obese, critically ill patient.

OBJECTIVE: To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM). CASE SUMMARY: A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53. DISCUSSION: High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function. CONCLUSIONS: Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.

[Necrotizing fasciitis. 2011 update]. / Nekrotisierende Fasziitis. Update 2011.

Necrotizing fasciitis belongs to a group of complicated soft tissue infections that can be even life threatening. Despite growing knowledge about its etiology, predictors, and the clinical progression, the mortality remains at a high level with 20%. A relevant reduction can be achieved only by an early diagnosis followed by consistent therapy. The clinical findings in about 75% of the cases are pain out of proportion, edema and tenderness, blisters, and erythema. It is elementary to differentiate a necrotizing or a non-necrotizing soft tissue infection early. In uncertain cases it can be necessary to perform a surgical exploration to confirm the diagnosis. The histopathologic characteristics are the fascial necrosis, vasculitis, thrombosis of perforating veins, the presence of the disease-causing bacteria as well as inflammatory cells like macrophages and polymorphonuclear granulocytes. Secondly, both the cutis and the muscle can be affected. In many cases there is a disproportion of the degree of local and systemic symptoms. Depending on the infectious agents there are two main types: type I is a polymicrobial infection and type II is a more invasive, serious, and fulminant monomicrobial infection mostly caused by group A Streptococcus pyogenes.Invasive, severe forms of streptococcal infections seem to occur more often in recent years. Multimodal and interdisciplinary therapy should be based on radical surgical débridement, systemic antibiotic therapy as well as enhanced intensive care therapy, which is sometimes combined with immunoglobulins (in streptococcal or staphylococcal infections) or hyperbaric oxygen therapy (HBOT, in clostridial infections). For wound care of extensive soft tissue defects vacuum-assisted closure has shown its benefit.

[Definition and management of wound infections]. / Definition und Management der Wundinfektion.

Surgical site infections (SSI) in the postoperative period represent the sword of Damocles in surgery. In spite of the medical progress in recent years these infections cannot always be avoided and occur in 25% of all nosocomial infections in Germany. They also generate up to 50% of the required costs in this context. The consequences vary from extended duration of hospitalization to elevated mortality. The degree of contamination of surgical wounds is of great importance as well as the patient's immune status and comorbidities. Prevention of infected surgical wounds is essential and important measures should begin even prior to the surgical procedure. In addition, during and following the surgical procedure several standards have to be followed. Rapid confirmation of diagnosis and correct management of surgical site infections are essential for the course of the disease. This study provides information on development, prevention and therapy of surgically infected wounds.

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis.

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis ("flesh-eating disease"). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the DeltamtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

Inhibition of group A streptococcal infection by Melaleuca alternifolia (tea tree) oil concentrate in the murine model.

AIMS: To investigate the effect of a water-soluble Melaleuca alternifolia concentrate (MAC) on group A streptococcus (GAS; Streptococcus pyogenes)-induced necrotizing fasciitis. METHODS AND RESULTS: MAC pretreatment (1% and 2% v/v) was able to protect mice from GAS infection in an air pouch model. GAS-induced mouse death and skin injury were inhibited dose dependently by MAC. Administration of MAC at 6 h post-GAS infection partially delayed mouse death. Surveys of the exudates of the air pouch of MAC-treated mice revealed that the survival of infiltrating cells was prolonged, the bacteria were eliminated, and the production of inflammatory cytokines was inhibited. MAC could directly inhibit the growth of GAS in vitro, and the minimal inhibitory concentration (MIC) of MAC for GAS was determined as 0.05% v/v using the time-kill assay. Furthermore, a sub-MIC dose of MAC not only enhanced the bactericidal activity of RAW264.7 macrophage cells against GAS but also increased susceptibility of GAS for blood clearance. CONCLUSIONS: These results suggest that MAC may inhibit GAS-induced skin damage and mouse death by directly inhibiting GAS growth and enhancing the bactericidal activity of macrophages. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide scientific data on the use of MAC for the treatment of GAS-induced necrotizing fasciitis in the murine model.

El médico de familia como factor de riesgo / The family doctor as a risk factor

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Surveillance for hospital outbreaks of invasive group a streptococcal infections in Ontario, Canada, 1992 to 2000.

BACKGROUND: Streptococcus pyogenes can cause severe disease in the individual patient and dramatic hospital outbreaks. OBJECTIVE: To describe the epidemiology of hospital outbreaks of invasive group A streptococcal infection in order to understand the potential benefit of proposed outbreak investigation and management strategies. DESIGN: Prospective, population-based surveillance. SETTING: Short-term care hospitals in Ontario, Canada. PATIENTS: Persons with a positive culture for group A streptococcus from a normally sterile site between 1 January 1992 and 31 December 2000. MEASUREMENTS: Laboratory-based surveillance identified patients with nosocomial invasive group A streptococcal infection. Epidemiologic and microbiological investigations were used to detect transmission. RESULTS: Of 2351 cases of invasive group A streptococcal disease, 291 (12%) were hospital acquired. Twenty-nine (10%) nosocomial cases occurred as part of 20 outbreaks. Seventy percent (14 of 20) of outbreaks involved nonsurgical, nonobstetric patients. Community-acquired cases initiated 25% of outbreaks; most were cases of necrotizing fasciitis in patients admitted to the intensive care unit. Outbreaks were small (median, 2 cases [range, 2 to 10 cases]) and short (median duration, 6 days [range, 0 to 30 days]). The median time between the first 2 cases was 4.5 days. The most common mode of propagation was patient-to-patient transmission. A staff carrier was the primary mode of transmission in 2 (10%) outbreaks, but 1 or more health care workers were colonized with the outbreak strain in 6 of 18 (33%) other outbreaks. LIMITATIONS: Some outbreaks with 1 case of invasive disease may have been missed; advice provided to participating hospitals may have reduced the number and size of outbreaks. CONCLUSIONS: Practices to prevent hospital transmission of group A streptococci should include isolation of patients admitted to the intensive care unit with necrotizing fasciitis, investigation after a single nosocomial case, and emphasis on identifying and treating health care worker carriers on surgical and obstetric services and patient reservoirs on other wards.

Chitosan malate inhibits growth and exotoxin production of toxic shock syndrome-inducing Staphylococcus aureus strains and group A streptococci.

Previously, it has been shown that the polysaccharide chitosan inhibits the growth of gram-positive bacteria. In this study, chitosan malate was evaluated in broth and thin-film cultures for its effect on the growth and exotoxin production of toxic shock syndrome (TSS)-inducing Staphylococcus aureus (five strains, three producing TSS toxin 1 and one each producing enterotoxin B or C) and group A streptococci (three strains producing streptococcal pyrogenic exotoxin A). Also, the compound was evaluated in a rabbit subcutaneous Wiffle ball model for its ability to prevent S. aureus and group A streptococcal induction of TSS. Finally, chitosan malate was evaluated for its ability to prevent TSS and necrotizing fasciitis in rabbits after subcutaneous inoculation with microbes. Chitosan malate inhibited both bacterial growth and, at sub-growth-inhibitory concentrations, the production of exotoxins, in both broth and thin-film cultures. Rabbits treated with chitosan malate in implanted Wiffle balls were protected from prior challenge with TSS-inducing S. aureus compared to animals not receiving chitosan malate (P < 0.001) and group A streptococci (P < 0.005). Chitosan malate protected rabbits from the development of streptococcal TSS with necrotizing fasciitis (P < 0.01). The data suggest that use of this growth- and toxin-inhibitory compound may be able to reduce the severity of S. aureus and group A streptococcal mucous membrane and trauma-associated skin infections.

Streptococcal pyrogenic exotoxin A release, distribution, and role in a murine model of fasciitis and multiorgan failure due to Streptococcus pyogenes.

The role of streptococcal pyrogenic exotoxin A (SPEA) was evaluated in a murine model of fasciitis and multiorgan failure due to a toxigenic strain of Streptococcus pyogenes. Increased serum levels of SPEA at 15 and 21 h were associated with a survival time of <24 h. Levels of SPEA correlated with interleukin-6 levels. Immunostaining showed SPEA localized to renal and hepatic cells. Neutralizing rabbit antibody to SPEA was administered to mice challenged with S. pyogenes, but no effect on survival was observed. Vaccination of mice with recombinant SPEA enhanced mortality due to streptococcal infection, despite the development of neutralizing immunity to the toxin prior to infection. Hence, SPEA is produced systemically during S. pyogenes soft-tissue infection, and increased levels are associated with reduced survival. In this model, however, SPEA did not appear to play a dominant role in pathogenesis; passive immunization against SPEA was not protective, and active immunization enhanced mortality.