Investigation on the Effect of Dose, Frequency and Duration of Allergen Exposure on Development of Staphylococcal Infections in a Chronic Model of Canine Atopic Dermatitis

Canine atopic dermatitis (CAD) is chronic and frequently complicated by Staphylococcal infections. Understanding the role of allergen dose, frequency and duration of exposure in triggering infections requires a model. Most models elicit acute inflammation and do not mimic real-life disease. Here we describe the effects of allergen exposures on development of infections in a model of chronic CAD. Diagnosis of pyoderma was based on clinical signs and consistent cytology. Study 1 evaluated the role of duration of exposure keeping the daily dose constant (25 mg/day). The one-week protocol involved three exposures, 3 days in a row. The one-month protocol involved twice-weekly challenges for 4 weeks. The three-month protocol involved twice-weekly challenges for 12 weeks. Study 2 evaluated different daily doses while keeping constant the total weekly dose (25 mg) and duration (3 weeks). Low-dose used 5 mg/day for 5 days, each week. High-dose used 12.5 mg/day twice-weekly. In Study 1, the longer the exposure, the more dogs developed pyoderma (6/9 in the three-month study, 2/9 in the one-month and 0 in the one-week). In Study 2, low-dose daily exposure caused more infections (5/8) than high-dose infrequent exposure (0/8). It is concluded that low-grade, daily exposure for a long time is most relevant for development of staphylococcal infections.

793. Rifabutin Use in Staphylococcal Prosthetic Material Infections: A Case Series

Background Bacterial biofilm formation is of clinical concern among patients with staphylococcal infections involving prosthetic material. While rifampin has in-vitro, animal and clinical data to support its adjunctive role in these types of infections, its potent induction of multiple cytochrome P450 enzymes and P-glycoprotein transport system proteins can pose significant drug-drug interactions. Rifabutin has comparable in-vitro anti-staphylococcal activity but less drug-drug interaction potential than rifampin. However, minimal clinical data exists to support rifabutin use as adjunctive treatment of prosthetic infections. Methods This case series describes 7 patients who received adjunctive rifabutin for staphylococcal prosthetic material infections between February 2018 and January 2021 at Massachusetts General Hospital. The primary outcome of infection recurrence was defined as need for surgical intervention for suspected or proven recurrence infection within 6 months after starting rifabutin therapy. Incidence of adverse effects was the main secondary outcome. Results Most patients (6/7) had methicillin-sensitive S. aureus (MSSA) and one patient had S. epidermidis infection. Three patients had spinal fusion hardware infection, one patient had hardware-associated spinal osteomyelitis/ diskitis with epidural abscess, two patients had prosthetic joint infection, and one patient had MSSA bacteremia with left ventricular assistance device involvement. All patients except one underwent surgical management prior to starting rifabutin. Infection recurrence was noted in one of seven patients who required surgical washout. Adverse events were uncommon (n=1 treatment-related nausea, n=1 leukopenia). Conclusion This small case series suggests favorable outcomes with use of rifabutin instead of rifampin for staphylococcal infections with prosthetic material involvement. Disclosures Sandra B. Nelson, MD, UpToDate (Other Financial or Material Support, author)

DNA Repair in Staphylococcus aureus

Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequently become chronic or recurrent, demonstrating a remarkable ability of S. aureus to withstand the hostile host environment.

Clinical Utility of Molecular Tests for Guiding Therapeutic Decisions in Bloodstream Staphylococcal Infections: A Meta-Analysis

Background: Treatment of bloodstream staphylococcal infections (BSI) necessitates the prompt initiation of appropriate antimicrobial agents and the rapid de-escalation of excessive broad-spectrum coverage to reduce the risk of mortality. We, therefore, aimed to demonstrate the diagnostic accuracy of nucleic acid amplification tests (NAAT) for the identification of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) in clinically suspected patients.Methods: Until November 23, 2020, databases including PubMed, Scopus, Embase, and Web of Science were scanned for eligible studies. A bivariate random-effects model was used for meta-analysis of the 33 included studies obtained from 1606 citations, and pooled summary estimates with 95% confidence intervals (CI) were generated.Results: Twenty-three studies (n = 8,547) assessed NAAT accuracy for MSSA detection, while three studies (n = 479) evaluated MRSA detection in adults. The pooled NAAT sensitivity and specificity for MRSA in adults was higher [sensitivity: 0.83 (95% CI 0.59–0.96), specificity: 0.99 (95% CI 0.98–1.0)] as compared to MSSA [sensitivity: 0.76 (95% CI 0.69–0.82), specificity: 0.98 (95% CI 0.98–0.99)]. Similarly, eight studies (n = 4,089) investigating MSSA in pediatric population reported higher NAAT accuracy [sensitivity: 0.89 (95% CI 0.76–0.96), specificity: 0.98 (95% CI 0.97–0.98)] compared to adults. Among NAA tests, SeptiFast (real-time PCR, commercial) was frequently applied, and its diagnostic accuracy corresponded well to the overall summary estimates. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency.Conclusions: NAAT could be applied as the preferred initial tests for timely diagnosis and BSI management.

Effect of Ciprofloxacin on the Growth and Biofilm Formation Ability of Staphylococcus aureus

Staphylococcus aureus is part of the normal bacterial flora of the skin, intestine and upper respiratory tract of both humans and animals and has the potential of causing staphylococcal infections if there is a breach in the hosts’ defense mechanism. These infections could range from mild superficial skin infections to more severe and even fatally invasive diseases such as sepsis and toxic shock syndrome. The infectivity of S. aureus is attributed to its ability to withstand extreme conditions and its possession of various virulence factors. The aim of this project was to study the effect of ciprofloxacin on the growth and biofilm forming ability of CM10 strain of Staphylococcus aureus using time kill study, resazurin and live/dead staining of biofilms and Real-time polymerase chain reaction. The identity of the given CM10 strain was confirmed when the result of the API-Staph was in total accordance with the results obtained from the colony morphology and phenotypic characterization tests (Coagulase/protein A, Gram, and Catalase tests). CM10 strain of S. aureus was not susceptible to 0.25mg/L of ciprofloxacin used for the time kill experiment but was susceptible to a minimum inhibitory concentration of 0.5mg/L. The difference between the ciprofloxacin treated biofilms of CM10 strain and the untreated biofilms was significant (P<0.05) showing that ciprofloxacin has an adverse effect on the cells in the biofilm. The results of this study provide an insight on the growth as well as the biofilm forming ability of CM10 strain of Staphylococcus aureus. Ciprofloxacin has been shown to be an effective antibacterial against this strain of S. aureus by its inhibitory effect on the growth as well as biofilm forming ability of this strain of S. aureus. This information would assist in developing novel anti-biofilm therapies to help in the management of biofilm mediated infections thereby reducing the morbidity and mortality rate of staphylococcal infections.

Model-based comparative analysis of rifampicin and rifabutin drug-drug interaction profile

ABSTRACT: Rifamycins are widely used for treating mycobacterial and staphylococcal infections. Drug-drug interactions (DDI) caused by rifampicin (RIF) is a major issue. We used a model-based approach to predict the magnitude of DDI with RIF and rifabutin (RBT) for 217 cytochrome P450 (CYP) substrates. On average, DDI caused by low-dose RIF were twice more potent than those caused by RBT. Contrary to RIF, RBT appears unlikely to cause severe DDI, even with sensitive CYP substrates.

Staphylococcus aureus Infections in the Paediatric Intensive Care Unit: Illustrated Cases

Staphylococcus aureus is known to be one of the most common gram-positive microorganisms and an important pathogen associated with sepsis and toxic shock. We present four anonymized consecutive cases in a paediatric intensive care unit (PICU) to illustrate the different clinical manifestations of staphylococcal infections, including local infection versus systemic infection, toxic shock versus septic shock, and osteomyelitis. Eczema, short gut syndrome, and scald injury may be associated. Haematologic and coagulopathic abnormalities may be present. Prompt diagnosis and use of appropriate antimicrobial treatments is essential to reducing mortality and morbidity associated with staphylococcal infections.

Staphylococcal Infections: Host and Pathogenic Factors

In 1880, the Scottish surgeon Sir Alexander Ogston first described staphylococci in pus from a surgical abscess in a knee joint: “The masses looked like bunches of grapes” [...]