Deep-seated Infections Research Articles

Relationship between distal tibial transosseous wires and ankle joint synovium: A cadaveric analysis

Background: Distal tibial fractures are managed with external fixation techniques such as Ilizarov to prevent soft-tissue-related complications. In spite of adequate care in wire placement techniques, some cases experience synovitis of ankle joint, stiffness of joint due to pin-tract infections, and deep-seated infection. The accurate description of the ankle joint capsular and synovial recess anatomy is still not clear. The purpose of our study was to study the accuracy of the available guidelines for wire insertion by identifying the relationship between the ankle capsular attachments and the wires in an Indian population. Materials and Methods: 1.8-mm Ilizarov transosseous wires were inserted percutaneously through the distal fibula to tibia from posterolateral to anteromedial direction 2 cm above the joint line in 20 embalmed cadaveric limbs. Dissection of the ankle joint was performed after a dye was introduced into the joint capsule to look for the extent of synovium from the joint line, medial malleolus, and lateral malleolus by the visible bulging and color change of the membrane. Distance from the wire to the synovial extensions distally was measured with a vernier caliper. Results: The mean distance of synovial extension from the joint line, medial malleolus, and lateral malleolus were 20.2 mm, 30.8 mm, and 41.4 mm, respectively. Distal wire-to-synovial extension distance anteriorly was ± 0.2 mm. Wire-to-joint line distance after dissection was 20 mm. The proximal synovial extension was found to be in the 101% from the joint line to the wire. Conclusion: The synovial extensions were found to be close to the distal tibial transosseous wires. A minimum distance of 2.5–3 cm from the joint line proximally should be the safe extent for passing the wires to prevent the risk of synovitis.

Simultaneous Brucella breast and pacemaker infection.

Infection with Brucella spp. is endemic to the Middle East and the eastern Mediterranean basin. Brucellosis can mimic infectious and non-infectious febrile illnesses and therefore it can pose a diagnostic challenge. A wide range of deep-seated infections have been ascribed to brucellosis including breast abscesses and infections of prosthetic endovascular devices. The latter are usually rare but difficult to treat short of excision of the infected device. Here, we present the case of a middle-aged Lebanese woman who presented with simultaneous breast abscesses and a pacemaker infection due to brucellosis. To our knowledge, a similar manifestation has not been reported in the literature.

COMPARISON OF PRE-OPERATIVE PERITONEAL WASH AND DRAINAGE VERSUS URGENT LAPAROTOMY STRATEGY IN PATIENTS WITH LATE STAGE PERFORATION PERITONITIS. A RANDOMIZED CONTROLLED TRIAL

Peritonitis is inflammation of peritoneum which is most commonly due to generalized or localized infection. Secondary peritonitis is the commonest form and a large percent of them is due to perforation or impending gastrointestinal perforation. The prognosis depends on multiple factors by which Mannheim Peritonitis Index (MPI) appears to be more practical. This study aimed to assess the value of pre-operative aspiration of peritoneal fluid followed by peritoneal wash and drainage before proceeding to definitive surgery in patients with MPI score>20. This prospective study was conducted in Al-Hussein Teaching Hospital in Al Nasserya city and Basrah Teaching Hospital in Basrah city from October 2003 to July 2014. Each patient admitted to the emergency department in these hospitals with the provisional diagnosis of perforation peritonitis was evaluated with MPI score. If the score was less than 20; the patient managed with resuscitation and broad spectrum antibiotics for 2-3 hours then by definitive surgery while those with MPI more than 20 were randomly divided into two groups; the first were managed with 2-3 hours resuscitation with intra-venous fluid resuscitation and antibiotics followed by urgent surgical exploration (USE). The second group were managed with percutaneous peritoneal drainage (PPD) with aspiration of the fluid and then irrigation of the peritoneal cavity with isotonic saline and followed by a drainage with aid of the gravity through another catheter located in the right ileac fossa. Sixty two patients included in this study who fulfilled the criteria of perforation peritonitis and MPI score more than 20. Around half of them the score was between 26-30. Perforated peptic ulcer is the commonest etiology. The most common cause of their high MPI score is the late presentation and the evidence of organ failure. Renal failure is the most prevalent organ failed in both groups. The overall mortality is decreased in (PPD) group. Those with urgent surgical exploration(USE) showed no improvements in the pre-operative vital signs, prolonged operation time and a higher mortality and more severe post-operative complication than PPD group. In conclusion, the pre-operative percutaneous peritoneal aspiration of the fluid followed by peritoneal irrigation and drainage in patients with advanced stage perforation peritonitis is associated with a significant improvement in the pre-operative pulse rate and blood pressure, decrease in the operation time, a decrease in the overall mortality and deep seated wound infection and dehiscence but it is associated with a higher mortality in the first post-operative day.

Biological Suppression of Sugarcane Smut with Endophytic Bacteria

Smut disease caused by Sporisorium scitamineum is emerging as a major threat to sugarcane cultivation in both tropical and subtropical India. The pathogen is primarily transmitted through sett, many times as deep seated latent infection that warrants a unique strategy to control the pathogen at the place of localization. Hence in this study an attempt was made to explore the potential of endophytic bacteria as a biocontrol agent for the management of smut disease. About 119 endophytic bacteria isolated from internode, bud and root were screened in vitro for their antagonist potential against S. scitamineum and among them eight exhibited strong antagonistic potential with > 30% mycelial growth inhibition. Testing of these eight antagonists for their biocontrol potential in two independent glass house experiments identified four endophytic bacterial strains viz., ESS 9, ESR 3, ESR 7 and ESR 21 as consistent performers. In experiment-I, these four bacteria exhibited 100% smut suppression, while in experiment-II they exhibited 49–62% reduction in smut incidence over control. Testing of these four endophytes for biocontrol potential in field under artificially pathogen-inoculated condition showed that endophytes treatment not only reduced smut incidence but also delayed the initial occurrence of disease by 60 days. In field trial, the least incidence of smut was recorded in ESR 7 (14.8%)- and ESR 21 (16.6%)-treated plants, i.e., more than 50% reduction in smut incidence over control. These two endophytes also showed potential in improving germination, number of millable canes, yield and juice quality parameters, viz. brix and sucrose. The endophyte B. pumilus ESR 21- and B. axarquiensis ESR 7-treated plants recorded the highest yield of 85.2 and 82.4 kg/plot, respectively, when compared to just 52.2 kg/plot in smut pathogen-inoculated control and 68.3 kg/plot in healthy control.

1036. Whole Genome Sequencing Analysis of a Large Cohort of Staphylococcus epidermidis Blood Culture Positive Isolates From a Multicenter Clinical Trial

Background Staphylococcus epidermidis is a leading cause of healthcare-associated bacteremia, but the clinical course of S. epidermidis isolated from blood cultures ranges from contamination to serious deep seated infections. We tested the hypothesis that the genetic characteristics of S. epidermidis isolated from blood cultures are significantly associated with disease severity using whole genome sequencing (WGS).MethodsWe performed WGS of 163 S. epidermidis isolates from a large prospective multicenter, randomized control trial that assessed the safety and efficacy of algorithm-based treatment of patients with staphylococcal bacteremia (ClinicalTrials.gov #NCT01191840). Patient’s infection types were divided into simple (including possible contamination), uncomplicated and complicated bacteremia. Failure was defined as persistent signs and symptoms of infection at 72 hours, persistent bacteremia at 7 days, relapse, complications or overall mortality within 28 days of therapy. WGS was performed using Illumina Miseq, followed by in silico multi-locus sequence type identification and phylogenomic analysis using kSNP.ResultsOf the 163 isolates analyzed, 39 sequence types (STs) were identified with ST2 and ST5 isolates being most frequently identified (21% and 20%, respectively). ST2 and ST5 isolates were significantly more likely associated with uncomplicated and complicated infections rather than simple bacteremia (P = 0.01 by χ2 test). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteremia was an independent predictor of a complicated infection (odds ratio 4.28, 95% CI 1.36–13.42). Using WGS based branching points rather than sequence typing allowed for additional strengthening of the association of S. epidermidis genetic clustering and clinical infection types (figure). Although there was no significant difference in failure rates among patients infected with different STs, ST2/ST5 strains were significantly more likely to cause relapsing infections (85.7%, P = 0.02).ConclusionWGS could offer a prognostic tool in the management of S. epidermidis bacteremia. ST2 and ST5 strains may help predict a complicated bacteremia course which would warrant appropriate antimicrobial therapy. Disclosures T. L. Holland, Basilea: Consultant, Consulting fee. Motif Bio: Consultant and Scientific Advisor, Consulting fee. Theravance: Consultant, Speaker honorarium. Genentech: Consultant, Consulting fee. V. G. Fowler Jr., Debiopharm: Consultant, Consulting fee. Durata: Consultant, Consulting fee. Merck: Consultant and Scientific Advisor, Consulting fee. Cerexa/Actavis/Allergan: Grant Investigator, Grant recipient. Pfizer: Consultant and Grant Investigator, Consulting fee and Grant recipient. Advanced Liquid Logics: Grant Investigator, Grant recipient. NIH: Grant Investigator, Grant recipient. MedImmune: Consultant and Grant Investigator, Consulting fee and Grant recipient. Basilea: Consultant and Grant Investigator, Consulting fee and Grant recipient. Karius: Grant Investigator, Grant recipient. Contrafect: Consultant and Grant Investigator, Consulting fee and Grant recipient. Regeneron: Grant Investigator, Grant recipient. Genentech: Consultant and Grant Investigator, Consulting fee and Grant recipient. Affinergy: Consultant and Grant Investigator, Consulting fee and Grant recipient. Locus: Grant Investigator, Grant recipient. Medical Surface, Inc.: Grant Investigator, Grant recipient. Theravance: Consultant, Consulting fee and Speaker honorarium. Green Cross: Consultant, Speaker honorarium. Grifols: Consultant, Consulting fee. xBiotech: Consultant, Consulting fee. Achaogen: Consultant, Consulting fee. Medicines Co: Consultant, Consulting fee. Novartis: Consultant, Consulting fee. Novadigm: Consultant, Consulting fee. Bayer: Consultant, Consulting fee. Cubist: Consultant, Consulting fee. Debiopharm: Consultant, Consulting fee. Durata: Consultant, Consulting fee. I. Raad, The University of Texas MD Anderson Cancer Center: Shareholder, Licensing agreement or royalty. The Unversity of Texas MD Anderson Cancer Center: Shareholder, Dr. Raad is a co-inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed to Novel Anti-Infective Technologies LLC, in which UTMDACC and Licensing agreement or royalty.

1003. Clinical Implications of Emerging Nonvaccine-Serotype Invasive Pneumococcal Disease Among Adults in the Republic of Korea in the Era of Protein-Conjugated Pneumococcal Vaccine

BackgroundIn the Republic of Korea (ROK), protein conjugated vaccines (PCV13 and PCV10) in replacement of PCV7 have been used in children since 2010, and then included in the childhood national immunization program (NIP) in 2014. This study investigated indirect effect of PVCs on serotypes in PCV-naïve adult invasive pneumococcal disease (IPD) and its clinical implications.MethodsA prospective observational cohort study was conducted, through the serotype surveillance program following the NIP implementation of 23-valent pneumococcal polysaccharide vaccine (PPV23) for elderly population (≥65 years) from 2013 to 2015. Clinical data and pneumococcal isolates from adult IPD patients (≥18 years) were collected from 20 hospitals. Clinical characteristics were compared between vaccine-serotype (VT) and nonvaccine-serotype (NVT) groups.ResultsOf a total of 319 IPD patients enrolled, 189 cases (59.2%) were available for serotypes. Among them, the proportion of PCV-naïve cases was 99.5% (188/189) and 189 patients consisted of NVT (n = 64, 33.9%) and VT group (n = 125, 66.1%). Compared with the previous study in the ROK (2004–2010), the proportion of PCV13 serotypes was decreased (61.4% vs. 37.0%, P < 0.001) and PPV23 serotypes were stationary (71.5% vs. 65.6%), but NVT serotypes were increased (23.4% vs. 33.9%, P = 0.033) in our study. The most common serotype was 3 (20.8%) and 34 (23.4%) in VT and NVT group, respectively. VT group had more bacteremic pneumonia (72.0% vs. 48.4%, P = 0.002). There was no difference of the case fatality rate between NVT and VT groups (29.7% vs. 35.2%, P = 0.447). Multiple logistic regression analysis showed that chronic kidney disease (odds ratio [OR] 10.26, 95% confidence interval [CI] 1.94–54.44, P = 0.006), younger age of 18–49 years (OR 4.04, 95% CI 1.29–12.71, P = 0.017), deep-seated infection (OR 3.73, 95% CI 1.34–10.39, P = 0.012), meropenem resistance (OR 3.21, 95% CI 1.49–6.91, P = 0.003) were significantly associated with NVT-IPD cases.ConclusionOur study indicates that emerging and expanding NVT-IPD among adults, probably due to indirect herd effect of widespread use of pediatric PCV. Further changes of IPD serotypes might occur and IPD serotypes should be monitored for developing better pneumococcal vaccination policy.Disclosures All authors: No reported disclosures.

2329. Preliminary Safety and Effectiveness of Whole-Body MRI in Pediatric Patients With Persistent Bacteremia or Febrile Illness

BackgroundEarly recognition of deep seated infections (osteomyelitis and abscesses) in the pediatric population may be difficult, given nonspecific symptoms and signs but remains crucial in the management. There is increasing emphasis on ionizing radiation dose reduction, making whole-body MRI (WBMRI) with short TI inversion recovery (STIR) the advanced imaging modality of choice over bone scintigraphy and CT-scans.MethodsA retrospective chart review of pediatric patients, <19 years, at Palmetto Health, Columbia, SC who had WBMRI with infectious indications during 9/2011 to 12/2013 was performed. The aims of this research were to describe complications related to sedation/contrast, to determine what portion of patients had new evidence of deep seated infections and to obtain initial evidence for effectiveness of WBMRI.Results20 patients were included with male predominance (12; 60%). 9/20 patients < 12 months old and 4 between the ages of 12–70 months. The most common comorbidity was sickle cell syndrome (n = 6) and 16/20 patients had a recent/current central venous catheter. The reasons for imaging were fever (9, 45%), pain/swelling (5, 25%), and abnormal labs/imaging (6, 30%). 19 patients had other diagnostics studies prior to WBMRI, 17 of whom had ionizing radiation using studies (X-rays / CT scans). 10/19 also had additional trips to the radiology department for focal MRIs. Duration of sedation for WBMRI averaged 88 minutes, with propofol (10/14) being the most common agent used. No complications from the sedation or the MRI contrast were recorded. WBMRI found an average of 1–4 areas of osteomyelitis in 11 patients and up to 8 other locations of deep seated infections in 15 patients. 11/20 had post WBMRI surgical intervention of debridement/drainage. Gram-positive cocci were isolated from 10/17 patients with positive blood/tissue cultures. Of those, 6 were methicillin-resistant Staphylococcus aureus.ConclusionUtilized as an early imaging modality in pediatric patients with persistent bacteremia/fevers, WBMRI commonly facilitated timely definitive interventions while sparing the patient exposure to ionizing radiation. WBMRI with STIR was safe and is likely to be cost effective.Disclosures All authors: No reported disclosures.

1069. Predictive Factors for Metastatic Infection in Patients With Bacteremia Caused by Staphylococcus aureus

BackgroundMetastatic infections, such as infective endocarditis and pyogenic spondylitis, are very serious complications of Staphylococcus aureus bacteremia (SAB), because failure to identify metastatic infections may cause poor prognosis. The aim of the present study is to determine the predictive factors for metastatic infections of SAB.MethodsThis retrospective cohort study was conducted among patients with bacteremia due to S. aureus (including both methicillin-sensitive S. aureus and methicillin-resistant S. aureus: MSSA and MRSA) in The Jikei University Kashiwa Hospital. The study population comprised 125 adult patients with SAB between January 2014 and December 2017. Patients, that died or transferred within 3 months after the initial positive blood culture, were excluded, because metastatic infection was defined as deep-seated infection detected within 3 months after the initial positive blood culture. We analyzed several factors, including demographics, comorbidities, community acquisition, primary site of infection, persistent fever and laboratory data such as c-reactive protein (CRP) levels after treatment.ResultsSeventy-four patients met inclusion criteria of this study. The most common primary site of bacteremia was catheter-related [24 (32.4%) of 74]. Metastatic infection occurred in 22 (29.7%) of 74 patients, and spondylitis was most common, following psoas abscess. Of these, 11 infections (50% of 22) were community acquired. We did not find any significant differences in demographics and comorbidities, except central venous catheter-associated bloodstream infection, which was associated with low rate of metastatic infection. By multivariate analysis, the predictive factors associated with the development of metastatic infection were community onset of infection (OR 11.6; 95% CI 2.98–45.1; P < 0.001), persistent fever over 72 hours (OR 6.7; 95% CI 2.12–21.8; P = 0.001), and higher CRP levels (>3 mg/dL) lasting 2 weeks after the administration of appropriate antibiotics (OR 7.47; 95% CI 2.39–23.3; P < 0.001).ConclusionThis study demonstrated that additional diagnostic tests to identify metastatic infection should be performed, especially in the patients with community-acquired SAB, persistent fever or persistently high CRP levels after the administration of appropriate antibiotics.Disclosures All authors: No reported disclosures.

Sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteraemia: one step closer.

Published guidelines call for prolonged courses of intravenous (iv) antibiotics for the treatment of MRSA bloodstream infection (BSI) to ensure eradication of deep foci and decrease relapse risk. Sequential iv-to-oral antibiotic therapy has been successfully applied to other serious infections but has not been evaluated for MRSA BSI. To compare outcomes in adults completing MRSA BSI therapy with oral versus parenteral antibiotics in the outpatient setting [oral outpatient antibiotic therapy (OOAT) versus outpatient parenteral antibiotic therapy (OPAT)]. This was a single-centre, retrospective, cohort study between 2008 and 2018. The primary outcome was 90 day clinical failure (MRSA BSI recurrence, deep-seated MRSA infection or all-cause mortality). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). A total of 492 patients were included (70 OOAT, 422 OPAT). In general, OOAT patients had characteristics consistent with a lower risk of poor outcomes; however, after IPTW key prognostic factors were balanced. In IPTW-adjusted analysis, there was non-significant reduction in the rate of 90 day clinical failure in the OOAT group compared with the OPAT group [adjusted HR (aHR) 0.379, 95% CI 0.131-1.101]. In analyses restricted to pre-specified subgroups defined by index infection complexity and comorbidity burden, findings were consistent with the main analysis. Furthermore, OOAT patients had a significantly reduced rate of 90 day hospital readmission (aHR 0.603, 95% CI 0.388-0.937). We provide preliminary evidence that selected patients with MRSA BSI may have at least equivalent clinical outcomes with OOAT versus OPAT and provide support to ongoing and future studies evaluating oral antibiotics for MRSA BSI.

Hemagglutination ability and hemolytic activity of Trichosporon asahii.

Trichosporon asahii is a human fungal pathogen that causes deep-seated infections in immunocompromised patients. While the pathogenic mechanisms of T. asahii remain unknown, our previous studies indicate that adherent colony morphologies were generated from parent strains, which may contribute to their pathogenicity. In the present study, we analyzed the hemolytic and hemagglutination activities of T. asahii. We report that T. asahii cells demonstrate hemagglutination and hemolytic activities, and that cell surface molecules play a role in the hemagglutination activity of adherent strains. These observations suggest that hemagglutination and hemolysis may be one of the pathogenic mechanisms of T. asahii.

Pre-clinical Imaging of Invasive Candidiasis Using ImmunoPET/MR.

The human commensal yeast Candida is the fourth most common cause of hospital-acquired bloodstream infections, with Candida albicans accounting for the majority of the >400,000 life-threatening infections annually. Diagnosis of invasive candidiasis (IC), a disease encompassing candidemia (blood-borne yeast infection) and deep-seated organ infections, is a major challenge since clinical manifestations of the disease are indistinguishable from viral, bacterial and other fungal diseases, and diagnostic tests for biomarkers in the bloodstream such as PCR, ELISA, and pan-fungal β-D-glucan lack either standardization, sensitivity, or specificity. Blood culture remains the gold standard for diagnosis, but test sensitivity is poor and turn-around time slow. Furthermore, cultures can only be obtained when the yeast resides in the bloodstream, with samples recovered from hematogenous infections often yielding negative results. Consequently, there is a pressing need for a diagnostic test that allows the identification of metastatic foci in deep-seated Candida infections, without the need for invasive biopsy. Here, we report the development of a highly specific mouse IgG3 monoclonal antibody (MC3) that binds to a putative β-1,2-mannan epitope present in high molecular weight mannoproteins and phospholipomannans on the surface of yeast and hyphal morphotypes of C. albicans, and its use as a [64Cu]NODAGA-labeled tracer for whole-body pre-clinical imaging of deep-seated C. albicans infections using antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI). When used in a mouse intravenous (i.v.) challenge model that faithfully mimics disseminated C. albicans infections in humans, the [64Cu]NODAGA-MC3 tracer accurately detects infections of the kidney, the principal site of blood-borne candidiasis in this model. Using a strain of the emerging human pathogen Candida auris that reacts with MC3 in vitro, but which is non-infective in i.v. challenged mice, we demonstrate the accuracy of the tracer in diagnosing invasive infections in vivo. This pre-clinical study demonstrates the principle of using antibody-guided molecular imaging for detection of deep organ infections in IC, without the need for invasive tissue biopsy.

Ciprofloxacin: from infection therapy to molecular imaging.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (99mTc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with 99mTc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with 99mTc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.

NEMISIS Minimally Invasive Surgical Correction for Midfoot Charcot Arthropathy

Category: Diabetes Introduction/Purpose: The most common cause of Charcot Neuroarthropathy is diabetes. The incidence of diabetes continues to rise globally, with a significant socio-economic burden to both patient and society. Despite good total contact casting techniques, deformity and subsequent ulceration still occurs in this patient group. This make shoe-fitting challenging and the risk of subsequent ulceration increases. This in-turn increases the patients risk of amputation and mortality at five years. Conservative treatment is often protracted, with multiple clinic visits. The has a significant impact on the patients ability to work and quality of life. Open surgery carries a significant risk of poor wound healing and infection again with risk of ulceration. NEMISIS for mid-foot Charcot provides surgeons with a surgical technique for osteotomy, that protects the soft tissues. Methods: The surgical technique utilises Minimally Invasive Shanon and Wedge burrs to perform a biplanar closing wedge osteotomy to achieve a triplanar correction. This takes the tension off the soft tissues which ensures that there is still good tissue cover, without compromising the blood supply to the skin, therefore in theory reducing the risk of infection. Stabilisation is achieved with screws, beams and bolts, +/-medial column plating. Patients are immobilised in a Bholer walker for a period of 3 months post-op. The short to medium term results (3months to 3 years) are presented. Patients are followed up to asses for re-ulceration at the same site, different site, failure of metalwork, return to surgery. Results: 16 patients were followed-up. 14 were diabetics. 4 patients developed deep-seated infection, which required removal of the metal-work. 2 of these patients did not have recurrence of their deformity and progressed to orthotic foot-wear. 1 patient had recurrence of deformity with wound breakdown and is awaiting further surgery. 1 patient had removal of metalwork from midfoot and subsequently developed hind-foot deformity which was stabilised with a hind-foot fusion nail. 1 patient broke the medial beam and bolts and required revision surgery. 2 patients had recurrence of plantar exostosis which was managed with minimally invasive exostectomy. 1 patient had early stabilisation of mid-foot and had subsequent Charcot of the talus, managed conservatively. The remaining patients have not required revision surgery. There have been not amputations. Conclusion: NEMISIS Minimally Invasive Surgery for Mid-Foot Charcot is a promising surgical technique which may help to reduce infection rates and subsequent amputations. The technique is relatively straightforward to teach, but is currently limited by the size of the burrs. The technique however can be coupled with innovation in biologics to aid the surgeon further in trying to achieve a stable plantigrade foot that does not have recurrence of ulceration and deformity.

Liquid biopsy for infectious diseases: sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

Diagnosis of life-threatening deep-seated infections currently requires invasive sampling of the infected tissue to provide a microbiologic diagnosis. These procedures can lead to high morbidity in patients and add to healthcare costs. Here we describe a novel next-generation sequencing assay that was used to detect pathogen-derived cell-free DNA in peripheral blood of patients with biopsy-proven invasive fungal infections. The noninvasive nature of this approach could provide rapid, actionable treatment information for invasive fungal infections when a biopsy is not possible.

Galleria mellonella as a model system to study virulence potential of mucormycetes and evaluation of antifungal treatment.

Mucorales can cause cutaneous to deep-seated infections, mainly in the immunocompromised host, resulting in high mortality rates due to late and inefficient treatment. In this study, Galleria mellonella larvae were evaluated as a heterologous invertebrate host to study pathogenicity of clinically relevant mucormycetes (Rhizopus spp., Rhizomucor spp., Lichtheimia spp., Mucor spp.). All tested species were able to infect G. mellonella larvae. Virulence potential was species-specific and correlated to clinical relevance. Survival of infected larvae was dependent on (a) the species (growth speed and spore size), (b) the infection dose, (c) the incubation temperature, (d) oxidative stress tolerance, and (e) iron availability in the growth medium. Moreover, we exploited the G. mellonella system to determine antifungal efficacy of liposomal amphotericin B, posaconazole, isavuconazole, and nystatin-intralipid. Outcome of in vivo treatment was strongly dependent upon the drug applied and the species tested. Nystatin-intralipid exhibited best activity against Mucorales, followed by posaconazole, while limited efficacy was seen for liposomal amphotericin B and isavuconazole. Pharmacokinetic properties of the tested antifungals within this alternative host system partly explain the limited treatment efficacy. In conclusion, G. mellonella represents a useful invertebrate infection model for studying virulence of mucormycetes, while evaluation of treatment response was limited.

Recent Advances in the Treatment of Scedosporiosis and Fusariosis.

Species of Scedosporium and Fusarium are considered emerging opportunistic pathogens, causing invasive fungal diseases in humans that are known as scedosporiosis and fusariosis, respectively. These mold infections typically affect patients with immune impairment; however, cases have been reported in otherwise healthy individuals. Clinical manifestations vary considerably, ranging from isolated superficial infection to deep-seated invasive infection—affecting multiple organs—which is often lethal. While there have been a number of advances in the detection of these infections, including the use of polymerase chain reaction (PCR) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), diagnosis is often delayed, leading to substantial morbidity and mortality. Although the optimal therapy is controversial, there have also been notable advances in the treatment of these diseases, which often depend on a combination of antifungal therapy, reversal of immunosuppression, and in some cases, surgical resection. In this paper, we review these advances and examine how the management of scedosporiosis and fusariosis may change in the near future.

Clinically applicable irreversible electroporation for eradication of micro-organisms.

Irreversible electroporation (IRE) is utilized in interventional radiology to treat cancer patients. In this study we evaluated invitro the antimicrobial effect of IRE. We demonstrated that using IRE with clinically established parameters has a marked effect on pathogenic micro-organisms and is synergistic to antimicrobials when both are combined. Our results point to the potential of IRE as a treatment modality for deep-seated infections.

Appropriate Duration of Intravenous Treatment of Candidemia and Timing of Step Down to Oral Therapy in Non-neutropenic Patients.

In this review, we have analyzed the available literature pertaining to the total duration of intravenous (IV) therapy and the appropriate timing of step down to oral therapy in the management of candidemia. Overview of the guidelines and literature seem to indicate that a minimum of 14 days of antifungal therapy is required in the treatment of candidemia without deeply seated infection. However, this was never based on evidence. Furthermore, step down to oral therapy seems to be dependent on the clinical stability criteria of the patient with candidemia after 4 to 7 days of IV therapy. Further studies are required to evaluate the appropriate total duration of IV therapy, appropriate timing of step down to oral therapy and to validate the clinical criteria that would allow the switch to happen.

Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial.

ABSTRACTThe performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.)

Oritavancin for the Treatment of Daptomycin Nonsusceptible Vancomycin-Resistant Enterococci Osteomyelitis

Abstract Vancomycin-resistant enterococci (VRE) are a growing cause of health care–associated infections globally, and limited treatment options exist for invasive VRE infections. Daptomycin is commonly used with modest success in the treatment of deep-seated infections secondary to VRE; however, there is concern for the emergence of daptomycin nonsusceptible VRE, especially during protracted courses, as required in osteomyelitis. We report the clinical and microbiologic success of a once-weekly, 6-week course of oritavancin with therapeutic drug monitoring in the treatment of daptomycin nonsusceptible VRE osteomyelitis secondary to prosthetic hip replacement. Our data suggest favorable pharmacokinetics and no treatment-related adverse events with once-weekly dosing. This report provides compelling information for future studies of prolonged oritavancin regimens in deep-seated infections.