Comparison of two fluorescent probes in preclinical non-invasive imaging and image-guided debridement surgery of Staphylococcal biofilm implant infections

Implant-associated infections are challenging to diagnose and treat. Fluorescent probes have been heralded as a technologic advancement that can improve our ability to non-invasively identify infecting organisms, as well as guide the inexact procedure of surgical debridement. This study’s purpose was to compare two fluorescent probes for their ability to localize Staphylococcus aureus biofilm infections on spinal implants utilizing noninvasive optical imaging, then assessing the broader applicability of the more successful probe in other infection animal models. This was followed by real-time, fluorescence image-guided surgery to facilitate debridement of infected tissue. The two probe candidates, a labelled antibiotic that targets peptidoglycan (Vanco-800CW), and the other, a labelled antibody targeting the immunodominant Staphylococcal antigen A (1D9-680), were injected into mice with spine implant infections. Mice were then imaged noninvasively with near infrared fluorescent imaging at wavelengths corresponding to the two probe candidates. Both probes localized to the infection, with the 1D9-680 probe showing greater fidelity over time. The 1D9-680 probe was then tested in mouse models of shoulder implant and allograft infection, demonstrating its broader applicability. Finally, an image-guided surgery system which superimposes fluorescent signals over analog, real-time, tissue images was employed to facilitate debridement of fluorescent-labelled bacteria.

Bacterial infections

Bacterial meningitis occurs in many clinical situations, including spontaneous (the most important category), post-traumatic, and device-associated (relating to cerebrospinal fluid shunts and drains). Each of these is associated with a particular pattern of infecting organisms, clinical presentation, and outcome, but overall there is high morbidity and mortality. Spontaneous meningitis is the most important category. It can be divided into neonatal meningitis and meningitis of childhood and adulthood. Post-traumatic meningitis follows neurosurgery or fractures of the skull. Device-associated meningitis complicates the use of cerebrospinal fluid shunts and drains. Infection may also be considered as community acquired or nosocomial (hospital acquired or physician associated).

Risk Factors for Maternal Readmission with Sepsis

Objective Our primary objective was to identify risk factors for maternal readmission with sepsis. Our secondary objectives were to (1) assess diagnoses and infecting organisms at readmission and (2) compare early (<6 weeks) and late (6 weeks to 9 months postpartum) maternal readmission with sepsis. Study Design We identified our cohort using linked hospital discharge data and birth certificates for California deliveries from 2008 to 2011. Consistent with the 2016 sepsis classification, we defined sepsis as septicemia plus acute organ dysfunction. We compared women with early or late readmission with sepsis to women without readmission with sepsis. Results Among 1,880,264 women, 494 (0.03%) were readmitted with sepsis, 61% after 6 weeks. Risk factors for readmission with sepsis included preterm birth, hemorrhage, obesity, government-provided insurance, and primary cesarean. For both early and late sepsis readmissions, the most common diagnoses were urinary tract infection and pyelonephritis, and the most frequently identified infecting organism was gram-negative bacteria. Women with early compared with late readmission with sepsis shared similar obstetric characteristics. Conclusion Maternal risk factors for both early and late readmission with sepsis included demographic characteristics, cesarean, hemorrhage, and preterm birth. Risks for sepsis after delivery persist beyond the traditional postpartum period of 6 weeks.

Infection, sepsis, and multiorgan dysfunction syndrome

Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.

Infection, sepsis, and multiorgan dysfunction syndrome

Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.

Onychomycosis Infections

Background: Mycological culture is the traditional method for identifying infecting agents of onychomycosis despite high false-negative results, slower processing, and complications surrounding nondermatophyte mold (NDM) infections. Molecular polymerase chain reaction (PCR) methods are faster and suited for ascertaining NDM infections. Methods: To measure agreement between culture and PCR methods for identification of infecting species of suspected onychomycosis, single toenail samples from 167 patients and repeated serial samples from 43 patients with suspected onychomycosis were processed by culture and PCR for identification of 16 dermatophytes and five NDMs. Agreement between methods was quantified using the kappa statistic (κ). Results: The methods exhibited fair agreement for the identification of all infecting organisms (single samples: κ = 0.32; repeated samples: κ = 0.38). For dermatophytes, agreement was moderate (single samples: κ = 0.44; repeated samples: κ = 0.42). For NDMs, agreement was poor with single samples (κ = 0.16) but fair with repeated samples (κ = 0.25). Excluding false-negative reports from analyses improved agreement between methods in all cases except the identification of NDMs from single samples. Conclusions: Culture was three or four times more likely to report a false-negative result compared with PCR. The increased agreement between methods observed by excluding false-negative reports statistically clarifies and highlights the major discord caused by false-negative cultures. The increased agreement of NDM identification from poor to fair with repeated sampling along with their poor agreement in the single samples, with and without false-negatives, affirms the complications of NDM identification and supports the recommendation that serial samples help confirm the diagnosis of NDM infections.

Infection, sepsis, and multiorgan dysfunction syndrome

Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.

Infection, sepsis, and multiorgan dysfunction syndrome

Sepsis is the main cause of multiple organ failure and remains a concern because of the associated high morbidity and mortality. In recent years, important advances have been made in the understanding of the pathophysiology of sepsis. Sepsis and septic shock are the end result of complex interactions between infecting organisms and various elements of the host response. A key feature of the common sequence of organ failure is dysfunction of the cardiovascular system, including microcirculatory elements. Outcome improvement in sepsis is based on recognizing the process early and instituting effective therapies. The time window for intervention is relatively short, and treatment must promptly control the source of infection, restore haemodynamic homoeostasis, and support failing organ systems.

Molecular Determination of Mixed Infections of Dermatophytes and Nondermatophyte Molds in Individuals with Onychomycosis

Background Reports of mixed infections with nondermatophyte molds (NDMs) and dermatophytes in onychomycosis are rare, possibly owing to the inhibition of NDM growth during traditional culture. We sought to determine the prevalence of mixed infections in onychomycosis using molecular identification. Methods Molecular analyses were used to identify infecting organisms directly from at least two serial great toenail samples from each of the 44 patients. Results Mixed infections were present in 41% of the patients (18 of 44). A single coinfecting NDM was the most common mixed infection and was detected in 34% of patients with onychomycosis (15 of 44), with Fusarium oxysporum present in 14% (6 of 44), Scopulariopsis brevicaulis in 9% (4 of 44), Acremonium spp in 2% (1 of 44), Aspergillus spp in 4.5% (2 of 44), and Scytalidium spp in 4.5% (2 of 44). Mixed infections with two NDMs were found in 7% of patients (3 of 44). Conclusions Mixed onychomycosis infections may be more prevalent than previously reported.

Surgical pathology

Understanding of the fundamental processes of pathology is essential both to the understanding of how many surgical conditions arise and develop and to the vital role of appreciating the principles of how best to treat conditions. For example, the nature and behaviour of infecting organisms determines whether radical debridement of tissue or simple surgical drainage is required; the stage and grade of tumours influence not only the choice of surgical procedure but the use of adjuvant thera­pies. These ‘surgical’ pathologies are often seen as rather ‘old-fashioned’ compared to the emphasis on cell and molecular biology so often found in books describing medical specialities but they form the bulk of the processes of disease suffered worldwide and remain fundamental to the skilled practice of surgery today.