Invasive Soft Tissue Infections Research Articles

Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections.

Linezolid may be an option for severe group A Streptococcus (GAS) infections based on its potent in vitro activity and antitoxin effects, but clinical data supporting its use over clindamycin are limited. This study evaluated treatment outcomes in patients with severe GAS skin and soft tissue infections who received either linezolid or clindamycin. This retrospective single-center cohort study examined patients with GAS isolated from blood and/or tissue cultures with invasive soft tissue infection or necrotizing fasciitis who underwent surgical debridement and received linezolid or clindamycin for at least 48 hours. The primary outcome was percentage change in Sequential Organ Failure Assessment (SOFA) score from baseline through 72 hours of hospitalization. After adjustment for time to first surgical intervention among patients with a baseline SOFA score >0 (n = 23 per group), there was no difference in reduction of SOFA score over the first 72 hours in patients receiving clindamycin vs linezolid. In the entire cohort (n = 26, clindamycin; n = 29, linezolid), there was no difference in inpatient mortality (2% vs 1%) or any secondary outcomes, including duration of vasopressor therapy, intensive care unit length of stay, and antibiotic-associated adverse drug events. There was no difference in reduction of critical illness as measured by SOFA score between baseline and 72 hours among patients treated with clindamycin vs linezolid. Given its more favorable side effect profile, linezolid may be a viable option for the treatment of serious GAS infections and should be further studied.

Case Report: Pseudomonas can take a toll on a patient

Pseudomonas aeruginosa( P. aeruginosa) is an aerobic Gram-negativebacterium that is implicated in the development of severe systemic infections among pediatric patients. It is identified in hospitalized chronically ill pediatric patients in association with genitourinary, respiratory tract, and skin or soft tissue infections as well as severe and life-threating infection including sepsis. A variety of immunologic mechanisms play a vital role in the host defense mechanisms against invasive infections with P. aeruginosa. Rarely, specific inborn errors of immune function are implicated in deficiencies that predispose to invasive infections with P. aeruginosa. Innate immune function including germ-line encoded pattern recognition receptors such as toll-like receptors (TLRs) and their downstream signaling is vital in the host defense against P. aeruginosa through the generation of antimicrobial peptides, cytokines/chemokines, and shaping of adaptive immune responses. Herein, we describe a previously healthy two-year-old female with an invasive skin, soft tissue, and central nervous system infection secondary to P. aeruginosa. The invasive nature of this infection prompted a careful evaluation for an inborn error of immunity. Decreased cytokine response to agonists of TLRs was documented. Targeted sequencing of interleukin-1 receptor-associated kinase (IRAK)-4 documented a homozygous deletion of exons 8-13 consistent with IRAK-4 deficiency. This report provides a vital educative message in the existing scientific literature by underscoring the importance of considering inborn errors of immunity in all patients with severe P. aeruginosa infections. Functional assessments of immune function often in combination with sequencing can accurately assign a diagnosis in a timely fashion allowing for definitive treatment and the use of necessary supportive care.

Invasive Eyelid Infections by β-Hemolytic Streptococci of Serogroup A

Invasive soft tissue infections by Streptococcus pyogenes are rapidly progressive and potentially life-threatening infectious diseases. These can also affect the eyelid. Aggressive virulence factors and the synthesis of exotoxins can lead to complications, such as periorbital necrotizing fasciitis (PONF) and streptococcal toxic shock syndrome (STSS). The clinical picture is characterized by four patients with invasive eyelid infections. Photographic documentation, radiological imaging, laboratory and smear diagnostics and intravenous antibiotic therapy were performed on all patients according to the recommendations of the German Robert Koch Institute and the local infectiology board. In all patients, Streptococcus pyogenes was culturally detected in a direct swab. The antibiogram showed sensitivity to the common intravenous antibiotics. The time interval between symptom onset and presentation at the clinic was between two days and one week. All patients had high systemic inflammatory parameters on admission: Pat. 1: CRP 259 mg/l, leukocytes 20.1 giga/l; Pat. 2: CRP 375 mg/l, leukocytes 15.6 giga/l; Pat. 3: CRP 378 mg/l, leukocytes 38.7 giga/l; Pat. 4: CRP 483 mg/l, leukocytes 1.7 giga/l; normal values: CRP < 5 mg/l, leucocytes 4.4 - 11.3 giga/l. In Pat. 2 and 3, a periorbital necrotizing fasciitis was diagnosed due to rapidly progressing necrosis in the area of cutis and subcutis and systemic toxicity. Pat. 3 and 4 met the diagnostic criteria of STSS. Pat.2, 3 and 4 had to be relocated to an intermediate or intensive care unit with sepsis, despite immediate intravenous antibiotic therapy. Patient 3 underwent surgical debridement during the stay in the intensive care unit. Thanks to interdisciplinary management (ophthalmology, infectiology, ear, nose and throat medicine, internal medicine and intensive care medicine), all patients were finally discharged from our inpatient treatment in a significantly improved general condition. Invasive streptococcal infections represent a challenge in the daily routine of an ophthalmologist. Interdisciplinary management and immediate onset of high-dose intravenous antibiotic therapy are crucial for successful treatment.

Necrotizing fasciitis: a tertiary centre based study

Background: Necrotizing fasciitis is a limb or life-threatening, invasive soft-tissue infection, although known since ancient times was first described in 1871. The purpose of the present study is to analyze the clinical presentation, bacterial flora, predisposing and co-morbid conditions, surgical and resuscitative treatment and outcome of this soft tissue infection.Methods: This is a prospective, cross-sectional, clinical study which was conducted from May 2016 until April 2018. This study included 60 consecutive patients. Age, gender, clinical presentation, co-morbid conditions and predisposing factors and pus culture sensitivity, treatment given, and its outcome were recorded.Results: With a male female ratio of 2.33:1 and median age of 46, most involves site was lower limb. Most patients presented with history of trauma followed by swelling (100%), pain (91.67%), and pus discharge (48.33%). Group A streptococcus was the most common organism isolated in both monomicrobial (53.85%) and polymicrobial (63.83%) cultures. Diabetes was the most common co morbidity observed. Fasciotomy and debridement were the mainstay of treatment with amputation rate of 23.33% and a mortality of 25%.Conclusions: Timely surgical intervention in the form of fasciotomy and debridement along with correction of malnutrition and anemia can be crucial in saving lives and limbs.

Prevalence and molecular diversity of invasive Streptococcus dysgalactiae and Streptococcus pyogenes in a German tertiary care medical centre.

Prevalence of invasive ß-haemolytic streptococci (BHS) at a tertiary care hospital and molecular diversity of S. pyogenes and S. dysgalactiae was studied. Between 2012 and 2016, all blood culture sets (n = 55,839), CSF (n = 8413) and soft tissue (n = 20,926)samples were analysed for BHS positivity using HYBASE software. Molecular profiles of 99 S. pyogenes and S. dysgalactiae were identified by sequencing of M protein genes (emm types) and multiplex PCR typing of 20 other virulence determinants. Streptococci contributed to 6.2% of blood, 10.7% of CSF and 14.5% of soft tissue isolates, being among the most common invasive isolates. The overall rates of invasive S. pyogenes, S. agalactiae, S. dysgalactiae and S. pneumoniae were 2.4, 4.4, 2.1, and 5.3%. Whereas S. pneumoniae was 1.5% more common in CSF samples, BHS isolates were 2-fold and 11-fold higher in bacteraemia and invasive soft tissue infections. Genetic BHS typing revealed wide molecular diversity of invasive and noninvasive group A and group G BHS, whereas one emm-type (stG62647.0) and no other virulence determinants except scpA were detected in invasive group C BHS. BHS were important invasive pathogens, outpacing S. pneumoniae in bacteraemia and invasive soft tissue infections. The incidence of S. dysgalactiae infections was comparable to that of S. pyogenes even with less diversity of molecular virulence. The results of this study emphasise the need for awareness of BHS invasiveness in humans and the need to develop BHS prevention strategies.

Streptococcal toxic-shock syndrome due to Streptococcus dysgalactiaesubspecies equisimilis in breast cancer-related lymphedema: a case report

BackgroundBreast cancer-related lymphedema often causes cellulitis and is one of the most common complications after breast cancer surgery. Streptococci are the major pathogens underlying such cellulitis. Among the streptococci, the importance of the Lancefield groups C and G is underappreciated; most cases involve Streptococcus dysgalactiaesubspeciesequisimilis. Despite having a relatively weak toxicity compared with group A streptococci, Streptococcus dysgalactiaesubspeciesequisimilis is associated with a mortality rate that is as high as that of group A streptococci in cases of invasive infection because Streptococcus dysgalactiaesubspeciesequisimilis mainly affects elderly individuals who already have various comorbidities.Case presentationAn 83-year-old Japanese woman with breast cancer-related lymphedema in her left upper limb was referred to our hospital with high fever and acute pain with erythema in her left arm. She showed septic shock with disseminated intravascular coagulation. Blood culture showed positive results for Streptococcus dysgalactiaesubspeciesequisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She survived after successful intensive care.ConclusionsTo the best of our knowledge, this case represents the first report of Streptococcus dysgalactiaesubspeciesequisimilis-induced streptococcal toxic-shock syndrome in a patient with breast cancer-related lymphedema. Breast cancer-related lymphedema is a common problem, and we must pay attention to invasive streptococcal soft tissue infections, particularly in elderly patients with chronic disease.

A Review of Clinical Cases of Infection with Photorhabdus Asymbiotica.

The three recognised Photorhabdus species are bioluminescent Gram-negative bacilli of the family Enterobacteriaceae. They are all pathogenic to insects and form a symbiotic relationship with nematodes of the genus Heterorhabditis. P. luminescens and P. temperata are both harmless to humans whilst P. asymbiotica, on the other hand, is a human pathogen that is a symbiont of the newly described nematode vector, Heterorhabditis gerrardi. In this chapter, we review the epidemiological and clinical features of eighteen human cases of P. asymbiotica infection including fifteen from the published literature and three previously unreported cases. Human infection has been reported in the USA and Australia and probably occurs in other parts of Asia where it remains undocumented. Infection occurs most commonly in warmer months particularly after rainfall. Patients may have a history of recent exposure to sand or sandy soil. P. asymbiotica causes both locally invasive soft tissue infection and disseminated disease with bacteraemia. Soft tissue infection may be multifocal with involvement of more than one limb and the trunk. The organism is sensitive to a number of antibiotics in vitro, but treatment failures have been associated with the use of beta-lactams and aminoglycosides. We suggest treatment with a four-week course of an oral fluoroquinolone such as ciprofloxacin. The organism grows readily on standard media from specimens such as wound swabs, pus, blood and even sputum and can be identified in a clinical microbiology laboratory but the diagnosis needs to be considered. The correct diagnosis is most likely to be made where there is close cooperation between clinician and microbiologist.

Primary pyomyositis and disseminated septic pulmonary emboli: a reactivated staphylococcal infection?

Staphylococcal pyomyositis is a severe invasive soft tissue infection with high mortality rate that is increasingly being recognized even in temperate climates. In most cases predisposing factors are identified that include either source of skin penetration or/and impaired host immunocompetence. A case of primary, community-acquired pyomyositis of the left iliopsoas muscle in a 59-year-old immunecompetent woman, which was complicated with septic pulmonary emboli within 24h after hospital admission, is presented. The patient was subjected to abscess drainage under computed tomography guidance. Both pus aspiration and blood cultures revealed methicillin-susceptible Staphylococcus aureus. Given the absolute absence of predisposing factors and a remote history of staphylococcal osteomyelitis in the same anatomical region 53 years ago, reactivation of a staphylococcal soft tissue infection was postulated. Systematic review of the literature revealed a few interesting cases of reactivated staphylococcal infection after decades of latency, although the exact pathophysiological mechanisms still need to be elucidated.

Extensive Subcutaneous Emphysema Resembling Necrotizing Fasciitis

Necrotizing fasciitis is an aggressive, invasive soft tissue infection. Because it can rapidly progress to patient instability, prompt diagnosis followed by urgent debridement is critical to decreasing mortality. Despite the importance of early diagnosis, necrotizing fasciitis remains a clinical diagnosis, with little evidence in the literature regarding the effectiveness of diagnostic tools or criteria. Common clinical findings are nonspecific, including pain, blistering, crepitus, and swelling with or without fever and a known infection source.This article describes a patient who was transferred to the authors' institution from another hospital, where she had been taken following seizure activity and was treated with antibiotics for suspected cellulitis at the intravenous catheter placement site on her left dorsal hand. On admission to the current authors' institution, she presented with pain and swelling in the setting of significant left upper-extremity emphysema. She had undergone a left shoulder arthroscopy 4 weeks previously. Vital signs were within normal limits, and a preoperative chest radiograph was read as normal. The patient underwent an emergent fasciotomy, irrigation and debridement of the left upper extremity, and intravenous antibiotics for suspected necrotizing fasciitis. Intraoperative findings indicative of infection were absent, and a left apical pneumothorax was later found on postoperative chest imaging.In a stable patient with a normal chest radiograph on presentation who demonstrates upper-extremity crepitus suspicious for necrotizing fasciitis, a chest computed tomography scan may be indicated to rule out an intrathoracic source.

Zoonotic Disease Pathogens in Fish Used for Pedicure

Zoonotic Disease Pathogens in Fish Used for Pedicure

Wound infections secondary to snakebite in central Taiwan

There are very few microbiological data on wound infections following snakebites. The objective of this study was to investigate the treatment of secondary infection following snakebites in central Taiwan. Microbiological data and antibiotic sensitivity of wound cultures were retrospectively analyzed from December 2005 to October 2007 in a medical center in central Taiwan. A total of 121 snakebite patients participated in the study. Forty-nine (40.5%) subjects were bitten by cobra (Naja atra); 34 of them had secondary infection, and 24 of them (70.6%) needed surgical intervention. Cobra bites caused more severe bacterial infection than other snakebites. Morganella morganii was the most common pathogen, followed by Aeromonas hydrophila and Enterococcus. Gram-negative bacteria were susceptible to amikacin, trimethoprim/sulfamethoxazole, cefotaxime, cefepime, ciprofloxacin, and piperacillin/tazobactam. Enterococcus were susceptible to ampicillin, gentamicin, penicillin and vancomycin. It is reasonable to choose piperacillin/tazobactam, quinolone, second- or third-generation cephalosporin for empirical therapy following snakebite. Surgical intervention should be considered for invasive soft tissue infections.

Photorhabdus asymbiotica: Shedding Light on a Human Pathogenic Bioluminescent Bacterium

Photorhabdus asymbiotica is a gram-negative bacillus of the family Enterobacteriaceae. The bacterium displays the curious property of bioluminescence – the production of light without heat. It is recognized as a human pathogen in the United States and Australia, where it causes both locally invasive soft tissue infection and disseminated disease. In Australia, P. asymbiotica is vectored by the soil nematode Heterorhabditis gerrardi. The vector in the U.S. has not yet been identified, but it is likely to also be a Heterorhabditid nematode. Although it grows readily on conventional culture media, clinical microbiology laboratories may misidentify this pathogenic bacterium because of an over-reliance on commercial rapid identification systems.

Bacterial infection in association with snakebite: A 10-year experience in a northern Taiwan medical center

Microbiological data of secondary wound infections following snakebites is rarely reported in Taiwan. The objective of this study was to assess the secondary wound infection after venomous snakebites. We conducted a 10-year retrospective survey on patients admitted for venomous snakebites and microbiological data of wound cultures at a medical center in northern Taiwan. Between April 2001 and April 2010, 231 patients who experienced snakebites were included. Male predominated, accounting for 62.3% (144). The age range of patients was 4-95 years. Ninety-five (41.1%) people were bitten by Trimeresurus mucrosquamatus, followed by Tstejnegeri, and cobra. A total of 61 pathogens were obtained from 21 patients. Thirty-nine (63.9%) isolates were gram-negative bacteria, 14 (23%) gram-positive pathogens, and 8 (13.1%) anaerobic pathogens. There were 17 patients bitten by cobra in these 21 patients. Morganella morganii and Enterococcus species were the most common pathogens identified in the wound cultures. Cobra bite causes more severe bacterial infection than other kinds of snakebites. Oral amoxicillin/clavulanate plus ciprofloxacin or parenteral piperacillin/tazobactam alone can be the choices for empirical or definitive treatment, and surgical intervention should be considered for established invasive soft tissue infections.

Necrotizing Fasciitis with No Mortality or Limb Loss

Necrotizing fasciitis is a potentially lethal invasive soft tissue infection. Early aggressive antibiotic therapy and surgical debridement have been the hallmark of successful therapy. It is commonly held that delays in surgical debridement significantly increase the mortality rate and rate of limb loss. A mortality rate of 20 per cent or greater has been reported throughout the last 80 years. We recently reviewed the cases of 20 consecutive patients admitted to our hospital in various stages of necrotizing fasciitis progression. Treatment of all 20 patients consisted of antibiotic therapy and surgical debridement, with frequent follow-up serial debridement. Topical negative pressure was achieved with the use of the Vacuum Assisted Closure system. An aggressive surgical approach, (including the frequency of debridement, appropriate antibiotic utilization, and use of the Vacuum Assisted Closure system), significantly impacted our results, despite delays in treatment and progression of the infection.

RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon

The CovR/S two-component system regulates the transcription of many genes that are crucial for the virulence of Streptococcus pyogenes (group A Streptococcus, GAS). Previously, we demonstrated that one gene repressed directly by CovR is rivR, which encodes a member of the RofA-like family of transcriptional regulators. In this study, we deleted rivR and its downstream gene rivX in a DeltacovR background. Microarray analysis revealed that the products of the rivRX locus exert positive control over the transcription of members of the Mga regulon. Using mutational analysis, we established that rivX encodes a small regulatory RNA. We found that RivR enhances transcriptional activation by Mga in vivo and in vitro. An M1 DeltacovRDeltarivRX strain is attenuated for virulence in a murine model of invasive soft tissue infection and this attenuation is complemented by rivRX expressed from a plasmid, demonstrating the importance of the rivRX locus in pathogenesis. This study provides the first link between the CovR and Mga regulatory networks. By integrating the signals received through these two global regulators, GAS is able to select from its repertoire different combinations of specific virulence factors to express in response to a broad spectrum of environmental conditions.

From insects to human hosts: Identification of major genomic differences between entomopathogenic strains of Photorhabdus and the emerging human pathogen Photorhabdus asymbiotica

Pathogenic bacteria of the genus Photorhabdus are naturally found in symbiotic association with soil entomopathogenic nematodes, and are of increasing economic interest in view of their potential for the development of novel biopesticides. This bipartite natural system is currently used for the biological control of crop pests in several countries. However, an increasing number of Photorhabdus strains have recently been isolated from human clinical specimens in both the United States and Australia, associated with locally invasive soft tissue infections and disseminated bacteraemia. In view of their growing use in biological control, which increases the potential rate of exposure of humans to these pathogens, we decided to undertake a comparative study of the genomic differences between insect and human pathogenic strains of Photorhabdus, in an attempt to understand the genetic mechanisms involved in the apparent change of host specificity, presumably responsible for their recently acquired capacity to infect humans. The data presented here demonstrates that major genomic differences exist between strains of Photorhabdus exhibiting virulence against insects or humans. Several individual genes, coding for virulence factors, were isolated and shown to be specific to the Photorhabdus asymbiotica human pathogens. One of these genes, sopB, encoding a host cell invasion factor translocated via the type III secretion system, has been cloned and the comparison of its genomic context in different pathogens strongly indicates that horizontal gene transfer is implicated in the acquisition of these virulence factors specific to the human pathogens. The precise role of this and other virulence factors identified here in the pathogenicity of P. asymbiotica towards humans is currently under investigation.

G群に凝集する&lt;I&gt;Streptococcus dysgalactiae&lt;/I&gt; subsp. &lt;I&gt;equisimilis&lt;/I&gt;による劇症型溶血レンサ球菌感染症の1例

Group G streptococcus (GGS) is infrequently associated with severe invasive soft tissue infection and toxic shock syndrome. A 74-year-old woman with a history of lymphedema of the lower extremities after surgical and radiation therapy for uterine cancer and diabetic mellitus and admitted for swelling of the right leg, fever, and dyspnea. She presented with shock and necrotizing cellulitis of the right lower extremity. Laboratory tests showed leukocytepenia, acute renal and liver dysfunction, and muscle damage. She rapidly developed multiple organ failure and necrotizing cellulitis. A swab from skin vesicle, throat, and blood culture grew Group G Streptococcus dysgalactiae subsp. equisimilis. Despite endotoxin hemoadsorption therapy, administration of antibiotics, and intravenous immunoglobulin, she died 9 days after admission due to toxic shock syndrome caused by GGS. The M-protein gene (emm) typing of GGS isolated from both blood and skin lesion showed stG 485.0. Three virulence genes, sagA, slo and skcg, were detected from GGS isolated from them.

Role of NADase in Virulence in Experimental Invasive Group A Streptococcal Infection

Group A streptococci (GAS) produce several exoproteins that are thought to contribute to the pathogenesis of human infection. Two such proteins, streptolysin O (SLO) and NAD(+)-glycohydrolase (NADase), have been shown to interact functionally as a compound signaling toxin. When GAS are bound to the surface of epithelial cells in vitro, SLO forms pores in the cell membrane and delivers NADase to the epithelial cell cytoplasm. In vitro, intoxication of keratinocytes with NADase is associated with cytotoxic effects and induction of apoptosis; however, the importance of NADase during infection of an animal host has not been established. We employed isogenic GAS mutants to assess the contribution of NADase activity to GAS virulence in vivo using mouse models of invasive soft-tissue infection and septicemia. In both models, mutant GAS that lacked NADase activity were significantly attenuated for virulence compared with the isogenic wild-type parent, confirming an important role for NADase in the infection of a host animal. A double mutant lacking SLO and NADase activity had an intermediate virulence phenotype, consistent with the hypothesis that SLO evokes a protective innate immune response. We conclude that NADase and SLO together enhance GAS virulence in vivo.

Cytolysin-dependent evasion of lysosomal killing

Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into lysosomes, where they were killed by a pH-dependent mechanism. Because SLO is the prototype of cholesterol-dependent cytolysins produced by many Gram-positive bacteria, cytolysin-mediated evasion of lysosomal killing may be a general mechanism to protect such pathogens from clearance by host epithelial cells.

Scedosporium apiospermumSoft Tissue Infection Successfully Treated with Voriconazole: Potential Pitfalls in the Transition from Intravenous to Oral Therapy

An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered a first-line antifungal agent. The potential usefulness of plasma voriconazole levels for guiding optimal therapy should be investigated.