John Emmanuel Markantonis

Corynebacterium species are a diverse group of organisms historically considered to be non-pathogenic, outside of the C. diphtheriae complex. Over the last few decades, this belief has been disproven with many notable non-diphtheriae Corynebacterium species being found to be pathogenic, often in certain clinical scenarios and/or anatomical sites. C. striatum and C. jeikeium are responsible for a large portion of bloodstream infections and orthopedic infections related to coryneform Gram-positive rods (GPRs). Eye and ear infections have commonly been attributed to C. macginleyi and C. otitidis , respectively. Pneumonia in critically ill and immunosuppressed individuals has been frequently reported by the C. propinquum / pseudodiphtheriticum group and occasionally in C. striatum. C. urealyticum is the primary pathogen associated with encrusted cystitis. Granulomatous lobular mastitis and breast abscesses have a strong association with C. kroppenstedtii . Erythrasma ( C. aurimucosum / minutissimum group), trichobacteriosis ( C. flavescens ), and hidradenitis suppurativa are cutaneous disorders caused by or associated with Corynebacterium species. Biofilm formation by these bacteria leads to hardware/medical device-associated infections involving endovascular catheters, cerebrospinal fluid shunts, peritoneal dialysis catheters, and prosthetic joints. Clinical microbiology laboratories must be aware of this and optimize laboratory identification and reporting of these organisms when appropriate. Matrix-associated laser/adsorption ionization time-of-flight mass spectrometry, currently available in most large clinical microbiology laboratories, offers laboratories the ability to rapidly, accurately, and affordably accomplish this task.

The recent increase in Group A Streptococcus (GAS) incidences in several countries across Europe and some areas of the Unites States (U.S.) has raised concerns. To understand GAS diversity and prevalence, we conducted a local genomic surveillance in Eastern North Carolina (ENC) in 2022–2023 with 95 isolates and compared its results to those of the existing national genomic surveillance in the U.S. in 2015–2021 with 13,064 isolates. We observed their epidemiological changes before and during the COVID-19 pandemic and detected a unique sub-lineage in ENC among the most common invasive GAS strain, ST28/emm1. We further discovered a multiple-copy insertion sequence, ISLgar5, in ST399/emm77 and its single-copy variants in some other GAS strains. We discovered ISLgar5 was linked to a Tn5801-like tetM-carrying integrative and conjugative element, and its copy number was associated with an ermT-carrying pRW35-like plasmid. The dynamic insertions of ISLgar5 may play a vital role in genome fitness and adaptation, driving GAS evolution relevant to antimicrobial resistance and potentially GAS virulence.

Pulmonary actinomycosis is an uncommon clinical entity that can be challenging to diagnose due to its non-specific symptomatology. Misdiagnosis and delayed treatment may result in invasive procedures and extended antimicrobial treatment courses. We report a case involving a 65-year-old female with poor oral dentition admitted for acute respiratory failure subsequently found to have a left-sided pleural effusion and perihepatic abscess formation. Cytopathology examination and microbiology studies confirmed the diagnosis of pulmonary actinomycosis.

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

Clostridioides difficile infection (CDI) is a leading nosocomial infection, posing a substantial public health challenge within the United States and globally. CDI typically occurs in hospitalized elderly patients who have been administered antibiotics; however, there has been a rise in the occurrence of CDI in the community among young adults who have not been exposed to antibiotics. C. difficile releases toxins, which damage large intestinal epithelium, leading to toxic megacolon, sepsis, and even death. Unfortunately, existing antibiotic therapies do not always prevent these consequences, with up to one-third of treated patients experiencing a recurrence of the infection. Host factors play a crucial role in the pathogenesis of CDI, and accumulating evidence shows that modulation of host immune responses may potentially alter the disease outcome. In this review, we provide an overview of our current knowledge regarding the role of innate and adaptive immune responses on CDI outcomes. Moreover, we present a summary of non-antibiotic microbiome-based therapies that can effectively influence host immune responses, along with immunization strategies that are intended to tackle both the treatment and prevention of CDI.

Background: Sickle cell disease (SCD) patients with a history of stroke are encouraged to receive chronic red blood cell exchange (RBCx) for stroke prevention. The American Society of Hematology guideline published in 2020 recommends an HbS target of <30%. However, this approach necessitates more frequent RBCx and more RBC units. UT Southwestern has devised a chronic exchange protocol that elevates the HbS target to <50% in patients with a low risk of stroke. Study Design: This retrospective chart review study reviewed the medical records of patients receiving chronic RBCx with a target of HbS <50% over the past 10‐year period to assess the safety of maintaining higher HbS targets in SCD patients with a low risk of cerebrovascular accidents (CVA). Results: Among 49 SCD patients in the chronic RBCx program for secondary stroke prevention, 33 patients were maintained on an HbS target of <50% (average measured: 35.4%) for the duration of RBCx program enrollment (median 93.0 months, 95% CI, 83‐99). Stroke or transient ischemic attack (TIA) clearly attributable to changing target HbS had not been identified among the 33 study subjects. Seven patients experienced conversion between the HbS targets of <50% and <30% HbS target. Significant reductions were observed in the frequency of RBCx and usage of blood volume in four of them. Conclusion: The findings suggest that liberalizing the HbS target could confer clinical flexibility without increasing the risk of CVA in a selective population. Further studies to fully evaluate the potential benefits of this approach are indicated.

Deposits of chromium orthophosphate with a greenish-gold color and flaky texture have been reported in the past literature in tissues from metal-onpolyethylene total hips and more recently in metal-on-metal total hips. It has been suggested that these deposits may contribute to adverse local tissue reactions. The aim of this study was to characterize these corrosion products and the local tissue reaction to them in a group of revised hip tissues from modular total hips. Periprosthetic tissues from 13 modular hip arthroplasties were histologically examined and debris was characterized by size, shape, color, contacting cell histology, and the surrounding tissue histology. Tapers were examined for evidence of tribocorrosion at the femoral tapers using a visual corrosion scoring criteria. Yellow-gold or silvery-green elongated or roughly rectangular debris ranged in size from 27 to 240 μm in length. These particles were typically in contact with foreign-body giant cells or an encapsulating layer of fibrous tissue. The surrounding tissue was variable but usually included histiocytic inflammation. Necrosis, microgranuloma formation, and lymphocytic inflammation were seen but were not prominent features. The tapers were ranked moderate to severe on the visual corrosion scale, and there was evidence of corrosion products outside of the main contact zone, typically in a thin, dark band distal to the taper contact area. Although modular interface corrosion can produce particulate debris, this is rarely identified within retrieval tissues. Because we examined mostly metal-on-metal hips, the presence of metal from the bearings in these tissues precluded a clear interpretation of the local reaction to the chromium orthophosphate debris. More extensive examination of tissues associated with corroded tapers from polyethylene or ceramic bearings may provide more information on reactivity of these tribocorrosion products.

The lubrication of the cartilaginous structures in human joints is provided by a fluid from a specialized layer of cells at the surface of a delicate tissue called the synovial lining. Little is known about the characteristics of the fluids produced after a joint arthroplasty procedure. A literature review was carried out to identify papers that characterized the synovial lining and the synovial fluids formed after total hip or knee arthroplasty. Five papers about synovial lining histology and six papers about the lubricating properties of the fluids were identified. The cells making up the re-formed synovial lining, as well as the lining of interface membranes, were similar to the typical Type A and B synoviocytes of normal joints. The synovial fluids around joint replacement devices were typically lower in viscosity than pre-arthroplasty fluids but the protein concentration and phospholipid concentrations tended to be comparable, suggesting that the lining tissue function was preserved after arthroplasty. The widespread, long-term success of joint arthroplasty suggests that the lubricant formed from implanted joint synovium is adequate for good clinical performance in the majority of joints. The role the fluid plays in component wear or failure is a topic for future study.