Necrotising fasciitis with extensive necrosis caused by Lactobacillus: a case report.

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.

TLR1/2 orchestrate human plasmacytoid predendritic cell response to gram+ bacteria.

Gram+ infections are worldwide life-threatening diseases in which the pathological role of type I interferon (IFN) has been highlighted. Plasmacytoid predendritic cells (pDCs) produce high amounts of type I IFN following viral sensing. Despite studies suggesting that pDCs respond to bacteria, the mechanisms underlying bacterial sensing in pDCs are unknown. We show here that human primary pDCs express toll-like receptor 1 (TLR1) and 2 (TLR2) and respond to bacterial lipoproteins. We demonstrated that pDCs differentially respond to gram+ bacteria through the TLR1/2 pathway. Notably, up-regulation of costimulatory molecules and pro-inflammatory cytokines was TLR1 dependent, whereas type I IFN secretion was TLR2 dependent. Mechanistically, we demonstrated that these differences relied on diverse signaling pathways activated by TLR1/2. MAPK and NF-κB pathways were engaged by TLR1, whereas the Phosphoinositide 3-kinase (PI3K) pathway was activated by TLR2. This dichotomy was reflected in a different role of TLR2 and TLR1 in pDC priming of naïve cluster of differentiation 4+ (CD4+) T cells, and T helper (Th) cell differentiation. This work provides the rationale to explore and target pDCs in bacterial infection.

Cardiac Microlesions Form During Severe Bacteremic Enterococcus faecalis Infection.

Enterococcus  faecalis is a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremic E. faecalis infection in mice. The cardiac microlesions were identical in appearance to those formed by Streptococcus pneumoniae during invasive pneumococcal disease. However, E. faecalis does not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein A (DsbA) was found to be required for E. faecalis virulence in a Caenorhabditis elegans model and was necessary for efficient cardiac microlesion formation. Furthermore, E. faecalis promoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in proinflammatory cytokines, unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish that E. faecalis is capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.

High frequency of enterotoxigenic Bacteroides fragilis and Enterococcus faecalis in the paraffin-embedded tissues of Iranian colorectal cancer patients.

BACKGROUND: The association between specific bacteria and colorectal cancer (CRC) has been proposed. Only a few studies have, however, investigated this relationship directly in colorectal tissue with conflicting results. So, we aimed to quantitate Streptococcus gallolyticus, Fusobacterium spp, Enterococcus faecalis and enterotoxigenic Bacteroides fragilis (ETBF) in formalin-fixed and paraffin-embedded (FFPE) colorectal tissue samples of Iranian CRC patients and healthy controls. METHODS: A total of 80 FFPE colorectal tissue samples of CRC patients (n = 40) and healthy controls (n = 40) were investigated for the presence and copy number of above bacterial species using quantitative PCR. Relative quantification was determined using ΔΔCT method and expressed as relative fold difference compared to reference gene. RESULTS: Relative abundance and copy number of E. faecalis and ETBF were significantly higher in CRC samples compared to control group. E. faecalis was more prevalent than ETBF in tumor samples. Frequency of ETBF and E. faecalis in late stages (III/IV) of cancer was significantly higher than early stages (I/II). We did not detect a significant difference in abundance of S. gallolyticus and Fusobacterium spp between two groups. CONCLUSION: Our study revealed the higher concentration of E. faecalis and ETBF in FFPE samples of CRC patients than controls. However, additional investigations on fecal and fresh colorectal cancer tissue samples are required to substantiate this correlation.

Intravitreal injection of povidone-iodine for the treatment of vancomycin-resistant Enterococcus faecalis endophthalmitis in rabbit eyes.

The aim of this study was to investigate the efficacy of intravitreal povidone-iodine (PI) in the treatment of vancomycin-resistant Enterococcus faecalis (VRE) endophthalmitis. Fifty New Zealand white rabbits were divided into 5 groups (n = 10 in each group). After the induction of endophthalmitis using VRE (minimum inhibitory concentration [MIC] ≥ 40 µg/mL) in the right eye, Group A, B, C, and D received intravitreal injections of 0.1% PI, 0.3% PI, 0.05% vancomycin, and 0.5% vancomycin, respectively. Eyes in Group E were used as controls. Fundus photography, vitreous culture, electroretinography (ERG), and histologic examinations of the retina were conducted on day 14. A marked improvement in endophthalmitis was observed in Group A, B, C and D, compared to Group E. Fundus photographs showed mild vitreous opacities in Group A and B, and moderate vitreous opacity in Group C. All eyes in Group D had a clear vitreous. In vitreous culture, bacterial growth was found in 6 eyes (100, 200, 200, 400, 500, and 500 colony-forming units) in Group C, but not in Groups A, B, or D. ERG and histological examination also indicated intraocular damage in Group C. Our results show that intravitreal injection of PI, even at low concentrations, was effective for treatment of VRE endophthalmitis, although some vitreous opacity remained. Intravitreal vancomycin injection was also useful to treat resistant strains, if used at a higher concentration within the safety threshold.

Florid Bacillus cereus Infection of the Placenta Associated With Intrauterine Fetal Demise.

Bacillus cereus is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal infections, including sepsis, meningitis, and pneumonia. Non-gastrointestinal B. cereus infections have been identified in children, especially in neonates; however, there are no previously described cases of fetal demise associated with B. cereus placental infection. We present a case of acute chorioamnionitis-related intrauterine fetal demise of twin A at 17 weeks gestation, noted two days after selective termination of twin B. Histological examination revealed numerous gram-positive bacilli in placental tissue, as well as fetal vasculature, in the setting of severe acute necrotizing chorioamnionitis and subchorionitis, intervillous abscesses, acute villitis, and peripheral acute funisitis. Cultures of maternal blood and placental tissue both yielded growth of B. cereus. This case underscores the importance of B. cereus as a human pathogen, and specifically demonstrates its potential as an agent of severe intraamniotic and placental infection with poor outcomes for the fetus.

Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing.NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

Propionibacterium/Cutibacterium species-related positive samples, identification, clinical and resistance features: a 10-year survey in a French hospital.

A 10-year retrospective study of Propionibacterium/Cutibacterium-positive samples gathered from hospitalized patients was conducted at Nantes University hospital. A total of 2728 Propionibacterium/Cutibacterium-positive samples analyzed between 2007 and 2016 were included. Due to the implementation of MALDI-TOF identification in 2013, most non-Cutibacterium acnes isolates were identified a second time using this technology. Over that period, Cutibacterium acnes remained the most predominant species accounting for 91.5% (2497/2728) of the isolates, followed by Cutibacterium avidum (4.2%, 115/2728) and Cutibacterium granulosum (2.4%, 64/2728). Regarding the origin of samples, the orthopaedic department was the main Cutibacterium sample provider representing 51.9% (1415/2728) of all samples followed by the dermatology department (11.5%, 315/2728). Samples were recovered from various tissue locations: 31.5% (858/2728) from surgery-related samples such as shoulder, spine or hip replacement devices and 19.1% (520/2728) from skin samples. MALDI-TOF method revealed misidentification before 2013. Cutibacterium avidum was falsely identified as C. granulosum (n = 33). Consequently, MALDI-TOF technology using up-to-date databases should be preferred to biochemical identification in order to avoid biased species identification. Regarding antibiotic resistance, 14.7% (20/136) of C. acnes was resistant to erythromycin. 4.1% (41/1005) of C. acnes strains, 17.9% (12/67) of C. avidum strains and 3.6% (1/28) of C. granulosum strains were found resistant to clindamycin.

Abiotrophia defectiva as a cause of infective endocarditis with embolic complications in children.

Abiotrophia defectiva is a rare pathogen of infective endocarditis (IE) but is frequently involved in embolic complication and valvular dysfunction. IE caused by A. defectiva in children is poorly studied. This study reports four cases of A. defectiva IE in children and reviews previously reported five pediatric cases of A. defectiva IE. Most of the patients presented with a subacute course, with prolonged fever or atypical symptoms. Eight patients had embolic complications at presentation. All nine children were treated with combination antimicrobial therapy and six of them received surgical intervention. All patients recovered well without relapse. A. defectiva should be considered in children with infective endocarditis, especially in those with atypical presentations. As complications are frequent and more than half of the patients need surgical treatment, prompt diagnosis along with appropriate treatment is necessary.

The role of Enterococcus faecalis during co-infection with avian pathogenic Escherichia coli in avian colibacillosis.

Enterococcus spp. (ENT) are frequently co-isolated with avian pathogenic E. coli (APEC) from poultry with colibacillosis, a leading cause of flock mortality. Although largely overlooked, ENT may play an active role in these infections. To assess the frequency of ENT co-isolation in colibacillosis, cultures were collected from birds with gross lesions of omphalitis, polyserositis, and septicaemia over a 3-year period from three turkey flocks and three broiler flocks. In birds diagnosed with colibacillosis based on gross findings and isolation of E. coli, ENT were co-isolated with APEC in 35.7% (n = 41/115) of colibacillosis mortality and 3.7% of total mortality (n = 41/1122). Co-isolated APEC and ENT pairs (n = 41) were further characterized using antimicrobial resistance phenotyping and in vitro co-culture assays. E. faecalis (EF) was the most commonly co-isolated species (68% n = 28/41) and tetracycline resistance was the resistance phenotype most commonly found among APEC (51% n = 21/41) and ENT (93% n = 38/41). Under iron-restricted conditions, EF enhanced APEC growth in a proximity-dependent manner and APEC grown in mixed culture with EF exhibited a significant growth and survival advantage (P ≤ 0.01). In an embryo lethality assay, APEC co-infection with EF resulted in decreased survival of broiler embryos compared to mono-infections (P ≤ 0.05). These data demonstrate that EF augmented APEC survival and growth under iron limiting conditions, possibly translating to the increased virulence of APEC in broiler embryos. Thus, ENT co-infections may be a previously unrecognized contributor to colibacillosis-related mortality. Further investigations into the mechanism of this interaction are warranted. RESEARCH HIGHLIGHTS Enterococcus is frequently co-isolated with avian pathogenic E. coli (APEC). Enterococcus faecalis (EF) enhances survival of APEC in iron restricted conditions. EF co-infection increases APEC virulence in broiler embryos.

Conjugation of Different Immunogenic Enterococcal Vaccine Target Antigens Leads to Extended Strain Coverage.

Enterococci have emerged as important nosocomial pathogens due to their resistance to the most commonly used antibiotics. Alternative treatments or prevention options are aimed at polysaccharides and surface-related proteins that play important roles in pathogenesis. Previously, we have shown that 2 Enterococcus faecium proteins, the secreted antigen A and the peptidyl-prolyl cis-trans isomerase, as well as the Enterococcus faecalis polysaccharide diheteroglycan, are able to induce opsonic and cross-protective antibodies. Here, we evaluate the use of glycoconjugates consisting of these proteins and an enterococcal polysaccharide to develop a vaccine with broader strain coverage. Diheteroglycan was conjugated to these 2 enterococcal proteins. Rabbit sera raised against these glycoconjugates showed Immunoglobulin G titers against the corresponding conjugate, as well as against the respective protein and carbohydrate antigens. Effective opsonophagocytic killing for the 2 sera was observed against different E. faecalis and E. faecium strains. Enzyme-linked immunosorbent assays against whole bacterial cells showed immune recognition of 22 enterococcal strains by the sera. Moreover, the sera conferred protection against E. faecalis and E. faecium strains in a mouse infection model. Our results suggest that these glycoconjugates are promising candidates for vaccine formulations with a broader coverage against these nosocomial pathogens and that the evaluated proteins are potential carrier proteins.

A Case of Fulminant Bacillus cereus Lung Necrosis in a Preterm Neonate.

Bacillus cereus is a ubiquitous Gram-positive rod seldom considered pathogenic in clinical isolates. However, it possesses multiple virulence factors explaining why it has been linked to fulminant and pyogenic infections in vulnerable hosts. Its recovery from sterile samples in immunocompromised patients cannot be disregarded. Premature infants would fall into this category. We describe the case of a neonate born at 26 weeks of gestational age, who died of a rapidly progressive B. cereus necrotizing pneumonia following suspected nosocomial acquisition. The rapidity of his course and the autopsy findings of necrosis with minimal inflammation suggest a toxin-mediated process. Pathologists should be aware of this pathogen and obtain proper microbiological samples in the presence of such autopsy findings, as the diagnosis may have infection-prevention implications in health-care settings.

Performance enhancement of procalcitonin by high-sensitivity C-reactive protein at the optimal cutoff in predicting bacteremia in emergency department adult patients.

Pathogenic bacteremia portends a high mortality risk in adult patients admitted to an Emergency Department (ED). This study aims to investigate the effect of adding high-sensitivity C-reactive protein (hs-CRP) to procalcitonin (PCT) and lactate in predicting bacteremia, Gram-negative (GNB) and Gram-positive bacteremia (GPB), using the optimal cutoff derived from the receiver operating characteristics analysis. We evaluated the diagnostic measures, including the positive-test likelihood (LR+), the negative-test likelihood (LR-), and the diagnostic odds ratio (DOR) using a single-center retrospective analysis design. This Standards for Reporting Diagnostic-compliant study comprised 886 consecutive adults who were admitted to the ED in 2010; to this cohort, a 22.2% prevalence of true bacteremia was subsequently confirmed. At the cutoff of 3.9 µg/L, PCT had a DOR of 5.3 (95% confidence interval [CI]: 3.76-7.61) and LR + of 2.8 (95% CI: 2.3-3.4) in predicting overall bacteremia. Elevated PCT and lactate (cutoff at 2 mmol/L), increased the DOR and LR + to 6.3 (95% CI: 4.27-9.29) and 4.0 (95% CI: 3.1-5.2). The DOR and LR + were further improved to 7.1 (95% CI: 4.2-11.95) and 5.6 (95% CI: 3.7-8.6), respectively, when hs-CRP at the cutoff of 1238 nmol/L was added to PCT plus lactate. High-sensitivity CRP at the cutoff of 1,255 nmol/L can enhance the discriminative power raising DOR and LR + values for GPB. The elevation of hs-CRP at the optimal cutoff might improve the diagnostic performance to predict unspecified bacteremia and GPB, but not GNB.

Peptoniphilus asaccharolyticus - Commensal, pathogen or synergist? Two case reports on invasive Peptoniphilus asaccharolyticus infection.

Peptoniphilus asaccharolyticus are gram-positive anaerobic cocci (GPAC) usually found as commensals of the skin or in the setting of polymicrobial colonisation of chronic wounds and ulcers. However, its pathogenic potential in more severe, invasive infections such as bone, joint or blood stream infections remains unclear, with studies on underlying virulence factors still pending. In this case report we present two cases of P. asaccharolyticus-associated infections of the bone and joint as well as a review of the literature. The cases cast a new light on possible synergistic interactions between P. asaccharolyticus and more virulent aerobic bacteria as well as on its role as pathogen in severe mono-infection.

Finegoldia magna causing intramedullary thoracic spinal cord abscess in an infant.

Spinal intramedullary abscesses are rare and potentially devastating lesions. Infection is mostly caused by staphylococci. Anaerobes are rare and often polymicrobial. We report an unusual case of spinal cord intramedullary abscess in a 7-month-old infant with monomicrobial infection due to Finegoldia magna. She was found to have a missed congenital thoracic dermal sinus. The patient was treated with metronidazole and ceftriaxone for 8 weeks, and improvement of the infection was documented. Clinical awareness of patients at risk is crucial for early diagnosis and intervention. As detection methods continue to improve for Finegoldia magna, it is important to increase awareness of the pathogenic role of this organism.

Eggerthia catenaformis bacteremia in a patient with an odontogenic abscess.

Eggerthia catenaformis is a Gram-positive anaerobic rod, which has been rarely reported in human diseases. We report the second case of bacteremia due to this microorganism in an elderly patient. A 73-year-old man, without underlying diseases presented with fever, odynophagia and swelling of the cervical lymph node for several days. Culture of drained cervical fluid resulted in the isolation of Raoultella ornithinolytica and Streptococcus anginosus. Anaerobic blood cultures yielded a rare anaerobic microorganism, identified as Eggerthia catenaformis. No resistance to tested antimicrobials was documented. Treatment with drainage and several antibiotic regimens was established, and the general condition of the patient improved, at two months of follow-up.

Atopobium vaginae intrapartum bacteremia: A case report with a literature review.

Atopobium vaginae is an anaerobic Gram-positive bacterium recognized as a causative agent of bacterial vaginosis and associated with preterm delivery. Invasive infection and bacteremia have been rarely reported. We describe the case of a woman expecting her firstborn child who presented with a A. vaginae bacteremia during labor. Identification was performed using 16S rRNA gene sequencing. Both maternal and fetal outcomes were favorable due to the maternal treatment with amoxicillin-clavulanic acid. We identified three other cases in the literature with different fetal outcome. The genetic diversity of A. vaginae should be further explored in order to reveal potential strains with differential pathogenic potential.

Slackia exigua, an anaerobic Gram-positive rod and part of human oral microbiota associated with periprosthetic joint infection of the hip. First case and review of the literature.

We report on the first case of a periprosthetic joint infection with the anaerobic Gram-positive rod Slackia exigua as the causative agent. The bacterium is part of human oral microbiota and has so far mainly been associated with periodontal diseases.

Intra-peritoneal abscess after an abdominal hysterectomy involving Cutibacterium avidum (former Propionibacterium avidum) highly resistant to clindamycin.

Cutibacterium avidum is a gram-positive anaerobic rod belonging to the cutaneous group of human bacteria with preferential colonization of sweat glands in moist areas. The microorganism rarely cause disease, generally delayed prosthetic joint infections (PJIs). We describe the second case of intraperitoneal abscess by C. avidum after an abdominal surgery in an obese female patient and the first case after a non-prosthetic abdominal surgery due to a highly clindamycin resistant strain in a patient with underling conditions. The patient was successfully treated with surgical drainage and beta-lactam antibiotics. Although rare and apparently non-pathogenic, C. avidum may be involved in infections, especially in some high-risk patients with obesity who have undergone surgical incision involving deep folder of the skin. The microorganism was identified by phenotypic methods, MALDI-TOF MS and 16S rRNA gene sequencing. Susceptibility test should be performed in C. avidum because high level resistance to clindamycin could be present. We present a literature review of C. avidum infections.