Deep-seated Infections Research Articles

Monoclonal Antibodies Targeting Surface-Exposed Epitopes of Candida albicans Cell Wall Proteins Confer In Vivo Protection in an Infection Model.

ABSTRACTMonoclonal antibody (mAb)-based immunotherapies targeting systemic and deep-seated fungal infections are still in their early stages of development, with no licensed antifungal mAbs currently being available for patients at risk. The cell wall glycoproteins of Candida albicans are of particular interest as potential targets for therapeutic antibody generation due to their extracellular location and key involvement in fungal pathogenesis. Here, we describe the generation of recombinant human antibodies specifically targeting two key cell wall proteins (CWPs) in C. albicans: Utr2 and Pga31. These antibodies were isolated from a phage display antibody library using peptide antigens representing the surface-exposed regions of CWPs expressed at elevated levels during in vivo infection. Reformatted human-mouse chimeric mAbs preferentially recognized C. albicans hyphal forms compared to yeast cells, and increased binding was observed when the cells were grown in the presence of the antifungal agent caspofungin. In J774.1 macrophage interaction assays, mAb pretreatment resulted in the faster engulfment of C. albicans cells, suggesting a role of the CWP antibodies as opsonizing agents during phagocyte recruitment. Finally, in a series of clinically predictive mouse models of systemic candidiasis, our lead mAb achieved improved survival (83%) and a several-log reduction of the fungal burden in the kidneys, similar to the levels achieved for the fungicidal drug caspofungin and superior to the therapeutic efficacy of any anti-Candida mAb reported to date.

Hemophagocytic Lymphohistiocytosis Associated With Endocarditis: A Case Years in the Making.

Hemophagocytic Lymphohistiocytosis Associated With Endocarditis: A Case Years in the Making.

Multiplex size marker (YEAST PLEX) for rapid and accurate identification of pathogenic yeasts.

BackgroundMultiple yeast species can cause human disease, involving superficial to deep‐seated infections. Treatment of these infections depends on the accurate identification of causative agents; however, reliable methods are not available in many laboratories, especially not in resource‐limited settings. Here, a new multiplex assay for rapid and low‐cost identification of pathogenic yeasts is described.MethodsA two‐step multiplex assay named YEAST PLEX that comprises of four tubes and identifies 17 clinically important common to rare yeasts was designed and evaluated. The set also provides PCR amplicon of unidentified species for direct sequencing. The specificity of YEAST PLEX was tested using 28 reference strains belonging to 17 species and 101 DNA samples of clinically important non‐target bacteria, parasites, and fungi as well as human genomic DNA. The method was further analyzed using 203 previously identified and 89 unknown clinical yeast isolates. Moreover, the method was tested for its ability to identify mixed yeast colonies by using 18 mixed suspensions of two or three species.ResultsYEAST PLEX was able to identify all the target species without any non‐specific PCR products. When compared to PCR‐sequencing/MALDI‐TOF, the results of YEAST PLEX were in 100% agreement. Regarding the 89 unknown clinical isolates, random isolates were selected and subjected to PCR‐sequencing. The results of sequencing were in agreement with those of YEAST PLEX. Furthermore, this method was able to correctly identify all yeasts in mixed suspensions.ConclusionYEAST PLEX is an accurate, low‐cost, and rapid method for identification of yeasts, with applicability, especially in developing countries.

Streptococcus agalactiae meningitis presenting with cerebral infarction in an adult patient: Clinical case and review

Bacterial meningitis is an inflammation of the meninges associated with the invasion of bacteria. The etiologic agents vary by age group. Bacterial meningitis due to group B streptococcus (GBS) is common for the neonatal period but is deemed to be rare in adult patients. Since 2000, more than two-thirds of all cases occur in adults, which is becoming a growing problem worldwide. We present a rare case of GBS meningitis presented with cerebral infarction in an adult patient and briefly review the etiology and incidence of GBS infections in adults. There is an increasing incidence of cases in elderly patients, particularly in those with more medical comorbidities. Cerebral infarction as an adverse effect in bacterial meningitis is both a sign of severity and a predictor of a poor clinical outcome with a high mortality rate. Early recognition of the infection, a search for deep-seated infection, and early antimicrobial therapy are vital moments for successful management of the GBS disease.

Predictors and Outcomes of Healthcare-Associated Infections Caused by Carbapenem-Nonsusceptible Enterobacterales: A Parallel Matched Case-Control Study.

ObjectivesThe increasing incidence of carbapenem-nonsusceptible Enterobacterales as major pathogens in healthcare associated infections (HAIs) is of paramount concern. To implement effective prevention strategies against carbapenem-nonsusceptible Enterobacterales (CnSE) HAIs, it is crucial to identify modifiable factors associated with these infections. We identified risk factors for CnSE-HAIs, and compared clinical outcomes of CnSE-HAI and carbapenem-sensitive Enterobacterales (CSE)-HAI patients.MethodsWe conducted a multi-centre parallel matched case-control study in two 1700-bedded Singapore acute-care hospitals from 2014–2016. Patients with CnSE-HAIs and CSE-HAIs were compared to a common control group without HAIs (1:1:3 ratio), matched by time-at-risk and patient ward. Carbapenem nonsusceptible was defined as non-susceptibility to either meropenem or imipenem. Presence of healthcare associated infections were defined by the criteria provided by the European Centre for Disease Prevention and Control. Outcomes of CnSE-HAI and CSE-HAI patients were compared using multivariable logistic and cox regression; the models were adjusted for infection and treatment characteristics.ResultsEighty CnSE-HAI and 80 CSE-HAI patients were matched to 240 patients without HAIs. All CRE-HAIs patients had prior antibiotic exposure, with 44 (55.0%) with prior carbapenem exposure. The most common CnSE-HAIs were intra-abdominal infections (28.8%) and pneumonia (23.8%). The most common CnSE species was Klebsiella spp. (63.8%). In the risk factor analysis, presence of drainage devices [adjusted odds ratio (aOR), 2.19; 95% CI, 1.29 – 3.70] and prior carbapenem exposure (aOR,17.09; 95% CI, 3.06 – 95.43) independently predicted CnSE-HAIs. In the crude outcomes analysis, CnSE-HAI patients had higher all-cause in-hospital mortality and longer time to discharge compared to CSE-HAI patients. After adjusting for differences in receipt of antibiotics with reported susceptibility to the Enterobacterales, there was no significant difference in all-cause in-hospital mortality between the two groups (aOR, 1.76; 95% CI, 0.86–3.58). Time to discharge remained significantly longer in patients with CnSE-HAI (adjusted hazard ratio, 0.71; 95% CI, 0.51 – 0.98) after adjusting for disease severity, receipt of antibiotics with reported susceptibility and receipt of appropriate source control.ConclusionAppropriate management of deep-seated Enterobacterales infections and reducing exposure to carbapenems may reduce risk of CnSE-HAIs in Singapore. Efforts to improve antimicrobial therapy in CnSE-HAI patients may improve patient outcomes.

MicroPET imaging of bacterial infection with nitroreductase-specific responsive 18F-labelled nitrogen mustard analogues.

Bacterial infection and antibiotic resistance are serious threats to human health. This study aimed to develop two novel radiotracers, 18F-NTRP and 18F-NCRP, that possess a specific nitroreductase (NTR) response to image deep-seated bacterial infections using positron emission tomography (PET). This method can distinguish infection from sterile inflammation. 18F-NTRP and 18F-NCRP were synthesized via a one-step method; all the steps usually involved in tracer radiosynthesis were successfully adapted in the All-In-One automated module. After the physiochemical properties of 18F-NTRP and 18F-NCRP were characterized, their specificity and selectivity for NTR were verified in E. coli and S. aureus. The ex vivo biodistribution of the tracers was evaluated in normal mice. MicroPET-CT imaging was performed in mouse models of bacterial infection and inflammation after the administration of 18F-NTRP or 18F-NCRP. Fully automated radiosynthesis of 18F-NTRP and 18F-NCRP was achieved within 90-110min with overall decay-uncorrected, isolated radiochemical yields of 21.24 ± 4.25% and 11.3 ± 3.78%, respectively. The molar activities of 18F-NTRP and 18F-NCRP were 320 ± 40GBq/μmol and 275 ± 33GBq/µmol, respectively. In addition, 18F-NTRP and 18F-NCRP exhibited high selectivity and specificity for NTR response. PET-CT imaging in bacteria-infected mouse models with 18F-NTRP or 18F-NCRP showed significant radioactivity uptake in either E. coli- or S. aureus-infected muscles. The uptake for E. coli-infected muscles, 2.4 ± 0.2%ID/g with 18F-NTRP and 4.05 ± 0.49%ID/g with 18F-NCRP, was up to three times greater than that for uninfected control muscles. Furthermore, for both 18F-NTRP and 18F-NCRP, the uptake in bacterial infection was 2.6 times higher than that in sterile inflammation, allowing an effective distinction of infection from inflammation. 18F-NTRP and 18F-NCRP are worth further investigation to verify their potential clinical application for distinguishing bacterial infection from sterile inflammation via their specific NTR responsiveness.

The yapsin family of aspartyl proteases regulate glucose homeostasis in Candida glabrata

Invasive candidiasis poses a major healthcare threat. The human opportunistic fungal pathogen Candida glabrata, which causes mucosal and deep-seated infections, is armed with distinct virulence attributes, including a family of 11 glycosylphosphatidylinositol-linked aspartyl proteases, CgYapsins. Here, we have profiled total membrane proteomes of the C. glabrata wildtype and 11 proteases-deficient strain, Cgyps1-11Δ, by mass spectrometry analysis and uncovered a novel role for fungal yapsins in glucose sensing and homeostasis. Furthermore, through label-free quantitative membrane proteome analysis, we showed differential abundance of 42% of identified membrane proteins, with electron transport chain and glycolysis proteins displaying lower and higher abundance in Cgyps1-11Δ cells, compared with wildtype cells, respectively. We also demonstrated elevated glucose uptake and upregulation of genes that code for the low-glucose sensor CgSnf3, transcriptional regulators CgMig1 and CgRgt1, and hexose transporter CgHxt2/10 in the Cgyps1-11Δ mutant. We further elucidated a potential underlying mechanism through genetic and transcript measurement analysis under low- and high-glucose conditions and found CgSNF3 deletion to rescue high glucose uptake and attenuated growth of the Cgyps1-11Δ mutant in YPD medium, thereby linking CgYapsins with regulation of the CgSnf3-dependent low-glucose sensing pathway. Last, high ethanol production, diminished mitochondrial membrane potential, and elevated susceptibility to oxidative phosphorylation inhibitors point toward increased fermentative and decreased respiratory metabolism in the Cgyps1-11Δ mutant. Altogether, our findings revealed new possible glucose metabolism-regulatory roles for putative cell surface-associated CgYapsins and advanced our understanding of fungal carbohydrate homeostasis mechanisms.

Evaluation of daily anti-tubercular treatment in osteoarticular tuberculosis

Background: Management of osteoarticular tuberculosis is primarily based on pulmonary tuberculosis guidelines. Guidelines usually do not take into consideration specific organ system affection, though tube pathology and healing of affected organ is not the same. Therefore, routine guidelines are difficult to follow in osteoarticular tuberculosis and many treatment regimes are in vague. Therefore, routine tuberculosis (TB) treatment is not followed, and many regimes are in vague. The current study is undertaken to objectively evaluate daily drug regime in osteoarticular TB and has specific guidelines. Materials and Methods: Drug-sensitive osteoarticular TB cases were evaluated for daily anti-tubercular treatment (ATT) guided by clinical and radiological healing. Patients were categorized based on stage, severity, and site of infection. Vitamin C and iron were also included in the daily treatment regime. Ethambutol was included in the continuation phase. Outcomes in terms of radiological healing and duration of daily regimen were studied. Results: All patients at 6 months of daily ATT showed clinical improvement but persistent disease on imaging. On magnetic resonance imaging, 16 out of 52 patients showed worsening at 6 months. Earliest healing appeared at 8 months. Healing appears to be faster in surgically treated patients. There was no relapse till the shortest follow-up of 2 years. Conclusion: The directly observed treatment strategy (DOTS), three times a week, is enough in osteoarticular TB. Daily drug with a minimum duration of 9 months is necessary. Diagnosis is usually delayed due to deep-seated infections, hence advance diagnosis modalities and high index of suspicion help. The study does not encounter any case of drug resistance. Addition of vitamin C appears to increase effectiveness of drugs. Duration of ATT should be determined by the pre-treatment disease activity and response to ATT.

Clinical Utility and Cost Effectiveness of Long-Acting Lipoglycopeptides Used in Deep-Seated Infections among Patients with Social and Economic Barriers to Care.

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. There was no difference in clinical failure between the two cohorts (22% vs. 30%; p = 0.491). Six patients in the SOC cohort left against medical advice (AMA) prior to completing therapy. Among those who did not leave AMA, receipt of LaLGPs resulted in a decreased hospital length of stay by an average of 13.6 days. The average total healthcare-related cost of care was USD 295,589 in the LaLGP cohort compared to USD 326,089 in the SOC cohort (p = 0.282). Receipt of LaLGPs may be a beneficial treatment option for patients with deep-seated infections and socioeconomic factors who are not candidates for oral transition or OPAT.

Long Term Evaluation of Paraumbilical Hernioplasty by Onlay Technique

Objective: To evaluate long term results of paraumbilical hernioplasty by onlay technique. Material & Methods: This prospective study was started in Jan 2017 and completed in Oct 2021. A total number of 196 patients having paraumbilical hernia were included in the study by convenient sampling. Patients with recurrent, strangulated and obstructed hernia as well as patients with ulcerated skin over the hernia were excluded from the study. All the patients were operated under general anesthesia with muscle relaxants. A non-absorbable standard prolene mesh (15x15 cm or 30x30 cm) was used and fixed with prolene 3-0 suture. Redivac drain was used over the mesh for minimum of three days. After discharge, all the operated cases were advised to visit the outpatient department after one week, one month, three months, six months, one year and two years. Maximum follow-up was two years and minimum was one year to assess the long term complication including recurrence. Demographic data along with diagnosis, complication, were collected and analyzed with Excel 2019. Results: Total 196 patients were operated for paraumbilical hernia. From which 53 were male and 143 were female. Minimum age was 18 years old and oldest patient was 78 years old. Average age was 40.19± 10 years, median age was 38 years. Seroma was seen in 04 patients. Superficial wound infection was observed in 02 patient no deep-seated infection was reported in our study. During three months of follow-up, numbness was noted in 03 patients and 02 patients had pain at the operation site during manual work. After two years recurrence was observed in two female patients, who failed to control their weight. Conclusion: Paraumbilical hernia is very common presentation in female patients. In order to prevent complication of hernia like, incarceration, strangulation and obstruction, early repair of the hernia is recommended in all the cases. Onlay mesh hernioplasty is one of the safest techniques which is relatively easy procedure, has a short learning curve with promising results. It has a low recurrence rate. Keywords: Onlay Mesh hernioplasty, Paraumbilical Hernia, PUH.

PET-CT save a day in deep-seated infection

A 60-year-old female had implantation of Ventriculoperitoneal (VP) shunt a year ago after suffering from subarachnoid hemorrhage with hydrocephalus. She presented this time with colicky abdominal pain and high swinging fever. Abdominal XRay (Panel A) was suggestive of intestinal obstruction due to paralytic ileus, which was treated conservatively. However, her fever persisted despite multiple broad-spectrum antibiotics. Whole body computed tomography with contrast was unremarkable. Lumbar puncture was done in view of intermittent confusion plus ongoing fever, it showed elevated cerebrospinal fluid total protein and high white cell count but the culture was negative. Eventually 2-[18F]-Fluoro-2-Deoxy-D-Glucose (2-[18F]-FDG) Positron Emission Tomography–Computed Tomography (PET-CT) revealed a 1.1 X 2.1 X 3.1 cm hypermetabolic (SUV max 9.1) rim enhancing collection around the tip of VP shunt, confirming the diagnosis of VP shunt infection (Panel B and C). Ventriculoperitoneal shunt infections may present with vague symptoms which make the diagnosis elusive. PETCT serves an important role given its enhanced diagnostic sensitivity. The patient completely recovered after removal of the infected shunt. From multiple case studies, PET-CT has been an emerging imaging tool in diagnosing shunt related infections in case of moderate clinical suspicion when first line of diagnostic modalities could not identify sources of infection [1,2].

Diagnostic Challenge in Boy with Recurrent Meningitis

Recurrent infections in children ranging from simple condition as upper respiratory tract infection which may be normal in this age to more serious infection as in deep seated infection. Meningitis is one of serious infection. Recurrent meningitis must be taken seriously and looking for causes and appropriate management. The aim of this case report is to present a rare case with serious complication. The other issue is to increase the awareness of cerebrospinal leaks among general pediatrics and general practitioners.

44. Cost Effectiveness and Clinical Outcomes of Long Acting Lipoglycopeptides Used in Transitions of Care for Deep-Seated Infections

BackgroundDalbavancin and oritavancin are long-acting lipoglycopeptides (LaLGPs) FDA-approved for one-time only dosing for skin and skin structure infections. The use of these agents in serious, deep-seated infections requiring protracted antibiotic courses is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT).MethodsThis is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients who received a LaLGP were matched 1:1 to those who received standard of care (SOC) therapy by age (+/- 10 years), infection type, microorganism, and socioeconomic factor (e.g. persons who inject drugs, homelessness). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. Secondary outcomes included hospital length of stay and proportion of patients who left against medical advice (AMA).ResultsA total of 46 patients were included (23 per group). The most frequent indication was endovascular infection and the most common organism methicillin-resistant Staphylococcus aureus. The average length of stay was 22.9 days vs. 31.9 days in the LaLGP and SOC cohorts, respectively (p=0.153). The average total healthcare-related cost of care was USD &295,589 in the LaLGP cohort compared to &326,089 in the SOC cohort (p=0.282). LaLGPs were associated with a mean savings of &30,500 - &55,831 per patient (cumulative cost savings of &701,510). There was no difference in clinical failure between the two cohorts (22% vs. 30%; p=0.491). Nearly 26% of patients in the SOC cohort left AMA compared to 0% in the LaLGP cohort (p=0.022). ConclusionReceipt of LaLGPs may be a beneficial treatment option for patients with socioeconomic factors and deep-seated infections who are not candidates for oral transition or OPAT.Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)

157. A Multicenter, Mixed-Method Evaluation of Delayed Hospital Discharge in Patients with Invasive Candidiasis Receiving Echinocandins

BackgroundPatients with systemic candidiasis often receive prolonged echinocandin therapy in the inpatient or outpatient setting. Rezafungin is a novel echinocandin currently in clinical trials characterized by once-weekly dosing interval. In order to understand the potential benefit of rezafungin to facilitate earlier hospital discharge, the purpose of this project was to better understand barriers to discharge in patients with proven or suspected invasive candidiasis.MethodsElectronic health records from two large health systems (20+ hospitals) were reviewed to identify patients given an echinocandin. Patients given an echinocandin until hospital discharge were evaluated for outpatient use as well as barriers that prevented earlier discharge. Identified barriers were developed into a quantitative framework and a qualitative interview guide. Using a constant comparative method, the framework for hospital discharge barriers was constructed using a series of open-ended questions and axial coding to identify discharge barrier themes. Results were integrated to produce a mixed-method model.ResultsA total of 1,665 echinocandin courses were evaluated. Five hundred and thirty-four patients (32%) received echinocandin therapy until at least the day of hospital discharge of which 328 of 534 (61%) patients were either discharged to home or transferred to another facility. Significant predictors for outpatient echinocandin use were osteomyelitis (OR 4.07, 95% CI: 1.06-15.66; p=0.041) and other deep-seated infection (OR 4.44; 95% CI: 1.65-11.96; p=0.003). Stewardship analysis identified the majority of patients (54%) had the possibility for at least one day earlier discharge (potential earlier discharge:1.65±1.16 days). The quantitative model identified major barriers to be transition of care-, other medical care-, and infectious diseases-related. The qualitative model largely agreed with the quantitative model with additional psychosocial and health care access variables identified.ConclusionUsing a mixed method approach, barriers to hospital discharge and potential use of new antifungal therapies were identified. These data could be used to assist transitions of care in patients with invasive candidiasis.Disclosures Truc T. Tran, PharmD, Merck (Grant/Research Support) Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort.

Plasma metagenomic next-generation sequencing (mNGS) has the potential to detect thousands of different organisms with a single test. There are limited data on the real-world impact of mNGS and even less guidance on the types of patients and clinical scenarios in which mNGS testing is beneficial. A retrospective review of patients who had mNGS testing as part of routine clinical care at Texas Children's Hospital from June 2018-August 2019 was performed. Medical records were reviewed for pertinent data. An expert panel of infectious disease physicians adjudicated each unique organism identified by mNGS for clinical impact. There were 169 patients with at least one mNGS test. mNGS identified a definitive, probable or possible infection in 49.7% of patients. mNGS led to no clinical impact in 139 patients (82.2%), a positive impact in 21 patients (12.4%), and a negative impact in 9 patients (5.3%). mNGS identified a plausible cause for infection more often in immunocompromised patients than in immunocompetent patients (55.8% vs. 30.0%, P = 0.006). Positive clinical impact was highest in patients with multiple indications for testing (37.5%, P = 0.006) with deep-seated infections, overall, being most often associated with a positive impact. mNGS testing has a limited real-world clinical impact when ordered indiscriminately. Immunocompromised patients with well-defined deep-seated infections are likely to benefit most from testing. Further studies are needed to evaluate the full spectrum of clinical scenarios for which mNGS testing is impactful.

Antibacterial Sonodynamic Therapy: Current Status and Future Perspectives.

Multidrug-resistant bacteria have emerged in both community and hospital settings, partly due to the misuse of antibiotics. The inventory of viable antibiotics is rapidly declining, and efforts toward discovering newer antibiotics are not yielding the desired outcomes. Therefore, alternate antibacterial therapies based on physical mechanisms such as light and ultrasound are being explored. Sonodynamic therapy (SDT) is an emerging therapeutic approach that involves exposing target tissues to a nontoxic sensitizing chemical and low-intensity ultrasound. SDT can enable site-specific cytotoxicity by producing reactive oxygen species (ROS) in response to ultrasound, which can be harnessed for treating bacterial infections. This approach can potentially be used for both superficial and deep-seated microbial infections. The majority of the sonosensitizers reported are nonpolar, exhibiting limited bioavailability and a high clearance rate in the body. Therefore, targeted delivery agents such as nanoparticle composites, liposomes, and microbubbles are being investigated. This article reviews recent developments in antibacterial sonodynamic therapy, emphasizing biophysical and chemical mechanisms, novel delivery agents, ultrasound exposure and image guidance strategies, and the challenges in the pathway to clinical translation.

Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

Clinical Outcomes with Ertapenem for Pneumonia in Obese versus Nonobese Patients.

The objective of this study was to compare the rate of pneumonia resolution in obese (body mass index [BMI], ≥30 kg/m2) and nonobese (BMI, <30 kg/m2) patients treated with 1 gram ertapenem daily. In this retrospective cohort study, we evaluated patients treated at The Ohio State University Wexner Medical Center between 1 January 2015 and 31 August 2020. Patients were included if they were between 18 and 89 years old and received ertapenem for at least 48 hours for pneumonia treatment. Patients were excluded if they were pregnant, were incarcerated, had renal impairment, received antibiotics with Gram-negative activity for a significant period prior to or in addition to ertapenem, and had other concomitant deep-seated infections. The primary outcome of clinical resolution was defined as meeting any of the following three criteria in order of evaluations: discontinuation of antibiotics by day 8 of therapy, afebrile while on ertapenem in addition to a decrease in white blood cell count, or improvement on chest radiograph at day 7 of therapy. A multivariable logistic regression analysis was performed to examine the association between obesity and clinical resolution, while adjusting for proven confounders. There were 76 nonobese and 65 obese patients included. The median patient BMI was 23.7 kg/m2 (21.0 to 26.9) and 35.0 kg/m2 (32.8 to 39.8) for the nonobese and obese cohorts, respectively. Clinical resolution was achieved in 78% (59/76) of nonobese and 75% (49/65) of obese patients (P = 0.75) without an observed difference in the regression model. Outcomes were similar in obese and nonobese patients treated with 1 gram of ertapenem daily for pneumonia.

What Do We Know about Candida auris? State of the Art, Knowledge Gaps, and Future Directions.

Candida auris has unprecedently emerged as a multidrug resistant fungal pathogen, considered a serious global threat due to its potential to cause nosocomial outbreaks and deep-seated infections with staggering transmissibility and mortality, that has put health authorities and institutions worldwide in check for more than a decade now. Due to its unique features not observed in other yeasts, it has been categorised as an urgent threat by the Centers for Disease Control and Prevention and other international agencies. Moreover, epidemiological alerts have been released in view of the increase of healthcare-associated C. auris outbreaks in the context of the COVID-19 pandemic. This review summarises the current evidence on C. auris since its first description, from virulence to treatment and outbreak control, and highlights the knowledge gaps and future directions for research efforts.

Intermediate to long term results of stemless metaphyseal reverse shoulder arthroplasty: A five to nine year follow-up

BackgroundShoulder arthroplasty incidence is increasing as is the volume of revision surgeries. Revision surgery is easier if humeral bone stock is preserved with minimal bone defects and osteolysis. This has led to an increased focus on the development of various short stemmed and stemless implants which provides stable fixation whilst preserving humeral bone stock. PurposeTo review the medium to long term clinical and radiological outcomes, complications and survival rates of a stemless reverse shoulder prosthesis. Patients and methodPatients with a minimum follow-up of 60 months following a reverse stemless shoulder arthroplasty were deemed eligible. Clinical and radiological data on twenty-one patients operated between 2009 and 2014 were recorded prospectively. Survivorship and patient recorded symptoms with the end point of revision surgery were recorded. ResultsMean follow-up of 78 months (60–114 months). Mean range of active elevation was 136° (80–170°). Mean range of active abduction and active external rotation was 122° (70–170°) and 47° (10–75°) respectively. Mean Oxford score improved from 12 pre-operatively to 44 at final follow up (p < 0.0001). Mean Constant Murley Score improved from 18 to 72 (p < 0.0001). Mean ADLEIR score of 13 pre-operatively increased to 32 post-operatively (p < 0.0001). Notching was seen in 23.5% of cases and no radiolucent areas were observed around the glenoid component. There were two cases of post traumatic peri-prosthetic fractures that were managed conservatively and one case of deep-seated infection that required a washout. The survivorship at the most recent follow-up was 100%. ConclusionThe advantages of bone preservation with the stemless metaphyseal prosthesis combined with encouraging medium to long term clinical and radiological results are very promising, particularly with the improved post-operative patient satisfaction scores. This is the first study that reports the results with a minimum of 5 year follow-up and has the longest mean follow-up period. Clinical relevanceThe reverse stemless shoulder prosthesis is an effective and reliable option for elective shoulder arthroplasty.